钙离子通道(Ca_v1.3)的听觉功能及内耳主动听觉机理的研究
|
摘要
第一部分Cav1.3钙离子通道蛋白在大鼠耳蜗中的表达模式
目的：
研究Cav1.3钙离子通道蛋白在成年大鼠耳蜗组织中的表达和分布，了解其在听觉生理和病理中的作用。
方法：
应用免疫组织化学的方法检测Cav1.3钙离子通道蛋白在耳蜗组织中的分布，采用免疫印迹技术（westernbloting，WB）以及逆转录聚合酶链反应（reversetranscription-polymerasechainreaction，RT-PCR）检测Cav1.3钙通道蛋白在耳蜗不同组织间的表达情况。
结果：
免疫化学方法显示Cav1.3钙通道蛋白主要分布在成年大鼠毛细胞、螺旋神经节细胞、螺旋神经板缘细胞、血管纹细胞以及螺旋韧带上。RT-PCR以及WB的结果显示Cav1.3钙通道蛋白表达具有一定的组织特异性，在耳蜗和肾脏组织中均有表达，其中耳蜗组织中基底膜上最多，螺旋神经节次之，血管纹和前两者相比其表达的量相对较少。
结论：
初步揭示了Cav1.3钙通道蛋白在成年大鼠耳蜗不同组织中的分布和表达差异，为进一步的研究Cav1.3钙离子通道蛋白在听觉生理和病理中重要的作用提供了理论依据。
第二部分Cav1.3钙离子通道蛋白的年龄相关性表达下调与老年性耳聋的研究
目的:
研究Cav1.3钙离子通道蛋白在老年性耳聋小鼠耳蜗组织中的表达，探讨其在老年性耳聋发病中的作用。
方法:
培育4w,14w,24w,48w不同年龄段的C57/6J小鼠为实验对象，应用听性脑干反应（auditorybrainstemresponse，ABR）分别检测4、14、24、48周龄的C57BL/6小鼠的听力。免疫荧光方法观察Cav1.3在不同周龄小鼠内耳组织中的分布，采用免疫印迹技术（westernbloting，WB）检测Cav1.3蛋白在不同年龄小鼠内耳中表达。同时采用实时荧光定量PCR（Real-timeRT-PCR）检测其基因（CACNA1D）mRNA在内耳组织的年龄相关性表达。
结果:
Cav1.3主要分布在小鼠耳蜗内外毛细胞、螺旋神经节、螺旋韧带、血管纹、螺旋（板）缘细胞。14、24、48周龄小鼠与4周龄小鼠相比ABR反应阈值明显提高（p<0.05），48周龄C57小鼠同前三组小鼠相比，ABR反应阈值显著提高（p<0.01）。随着鼠龄的增长，Cav1.3表达含量逐渐减少（p<0.01）。
结论：老年性耳聋小鼠Cav1.3钙离子通道蛋白表达含量随年龄增长而减少，其功能的异常和缺失可能在老年性耳聋的发病中起一定的作用。
第三部分缝隙连蛋白26(Connexin26)在听觉功能中的作用及耳聋机制的研究
目的:
研究Connexin26在听觉功能以及内耳主动听觉机理中的作用，探讨Connexin26缺失引起耳聋的机制。
方法:
运用loxP-Cre技术敲除耳蜗DCs和OPCs上的缝隙连蛋白26(Cx26)的表达。由Cx26loxP/loxP转基因鼠和Prox1-CreERT2小鼠杂交培育缝隙连蛋白26选择性敲除小鼠（以下简称Cx26cKO小鼠）。分别检测野生型、杂合子以及纯合子不同基因型小鼠听性脑干反应（auditorybrainstemresponse，ABR）、微音器电位（CM）、畸变耳声发射（DPOAE）、内淋巴电位（EP）。免疫组织化学的方法检测Cx26、Cx30以及外毛细胞电能动性蛋白Prestin的表达。甲苯氨蓝染色观察不同基因型小鼠螺旋神经节差异。采用实时荧光定量PCR（Real-timeRT-PCR）检测Prestin在野生型和纯合子小鼠的表达。
结果:在缝隙连蛋白26选择性敲除小鼠耳蜗顶回、中回及底回的Deiters’细胞和外柱细胞上均没有Cx26的表达。Cx26在耳蜗其他组织如螺旋缘以及外侧壁的表达正常。而另外一种连接蛋白Cx30在耳蜗组织中的表达也正常。Cx26cKO小鼠有听力损失，听性脑干反应阈值增加以及DPOAE降低，但是微音器电位和内淋巴电位均正常。外毛细胞电能动性蛋白Prestin的表达也并无异常，内耳的毛细胞和螺旋神经节也未发现明显的损失和退变。
结论：耳蜗主动放大机理依赖于支持细胞的缝隙连接。缝隙连蛋白26功能的缺失可以减弱耳蜗放大器的功能从而引起听力的损失。
PART ONE Expression Patterns of Cav1.3calcium channels in the rat cochlea
Objective: To investigate the expression of Cav1.3calcium channels in the rat cochlea and study its role in auditory physiology and pathology.
Methods:The distribution of Cav1.3calcium channels in the rat cochlea was detected by immunohistochemistry. The expression of Cav1.3calcium channels was measured with western bloting (WB) and reverse transcription-polymerase chain reaction (RT-PCR).
Results:Immunohistochemistry revealed that Cav1.3calcium channels were localized in the outer hair cells (OHCs), inner hair cells (IHCs), limbus laminae spiralis, spiral ganglion cell, spiral ligament and stria vascularis. The results of RT-PCR and Western blotting demonstrated Cav1.3calcium channels had a tissue-specific expression pattern. Cavl.3mRNA and protein were intensively expressed in the basilar membrane and spiral ganglion while moderate level of Cavl.3was observed in spiral ligament and stria vascularis.
Conclusion:The study preliminary reveals the expression patterns of Cavl.3calcium channels in the rat cochlea, providing a theoretical basis for further research on the role of Cav1.3calcium channels in the periphery auditory system.
PART Two Downregulation of Cav1.3calcium channel expression in the cochlea is associated with Presbycusis in C57BL/6mice
Objective:To investigate the expression of Cav1.3calcium channel in C57BL/6mice cochlea and study its correlation with presbycusis.
Methods:Auditory function was measured with auditory brainstem response (ABR) in C57BL/6mice at4,14,24and48weeks. The expression of Cav1.3calcium channels was detected by immunofluorescence,Western Blotting and Real-time RT-PCR at various ages.
Results:Immunofluorescence photographs reveal that Cav1.3channels were mainly localized in the hair cell, spiral ganglion cell, spiral ligment, stria vascularis, spiral limbus. Comparing with4-week group, the ABR threshold of4-,24-, and48-week increased (p<0.05). The ABR threshold at48-week group was significantly higher than others (p<0.01). Along with age, the missing hair cells and spiral ganglion cells increased, stria vascularis and spiral ligament atrophied, the expression of Cav1.3channels was gradually decrease d(p<0.01).
Conclusion:The expression of Cav1.3channels decreased along with age. Dysfunction or missing of Cavl.3calcium channels may be related to presbycusis.
PART Three Contribution of connexin26to active cochlear amplification and underlying mechanisms for connexin26deficiency induced hearing loss
Objective:To investigate Connexin26hearing function and contribution to active cochlear amplification and deafness mechanisms underlying Cx26deficiency induced hearing loss.
Methods:We used loxP-Cre technique to delete Cx26expression in Deiter cells (DCs) and outer pillar cells (OPCs). The Cx26conditional knockout (cKO) mouse was generated by crossing Cx26loxP/loxP transgenic mice with a Proxl-CreERT2mouse line. Auditory function was measured with auditory brainstem response (ABR), DPOAE, CM and EP in Cx26cKO mice. The expression of Cx26, Cx30and Prestein were detected by immunofluorescence staining. Consecutive cochlear paraffin sections were stained with toluidine blue to account SG neuron. Prestin expression at the transcriptional level was measured by real-time RT-PCR.
Results:Cx26labeling was absent in DCs and OPCs in Cx26cKO mice. The deletion of Cx26is visible in all three apical, middle, and basal turns. Cx26labeling in other cochlear structures, including the spiral limbus (SLM) and the lateral wall, remained normal. Cx30, which is another predominant connexin isoform in the cochlea, also retained normal expression. Targeted-deletion of Cx26in DCs and OPCs induced hearing loss The ABR threshold in homozygous mice was increased significantly and DPOAE was significantly reduced. CM and EP in Cx26cKO mice were normal. No reduction in prestin. No apparent cell degeneration in the Cx26cKO mouse cochlea.
Conclusion:The study demonstrates that active cochlear amplification in vivo is dependent on supporting cell gap junctions. These new findings also show that connexin26deficiency can reduce active cochlear amplification to induce hearing loss.
目的：
研究Cav1.3钙离子通道蛋白在成年大鼠耳蜗组织中的表达和分布，了解其在听觉生理和病理中的作用。
方法：
应用免疫组织化学的方法检测Cav1.3钙离子通道蛋白在耳蜗组织中的分布，采用免疫印迹技术（westernbloting，WB）以及逆转录聚合酶链反应（reversetranscription-polymerasechainreaction，RT-PCR）检测Cav1.3钙通道蛋白在耳蜗不同组织间的表达情况。
结果：
免疫化学方法显示Cav1.3钙通道蛋白主要分布在成年大鼠毛细胞、螺旋神经节细胞、螺旋神经板缘细胞、血管纹细胞以及螺旋韧带上。RT-PCR以及WB的结果显示Cav1.3钙通道蛋白表达具有一定的组织特异性，在耳蜗和肾脏组织中均有表达，其中耳蜗组织中基底膜上最多，螺旋神经节次之，血管纹和前两者相比其表达的量相对较少。
结论：
初步揭示了Cav1.3钙通道蛋白在成年大鼠耳蜗不同组织中的分布和表达差异，为进一步的研究Cav1.3钙离子通道蛋白在听觉生理和病理中重要的作用提供了理论依据。
第二部分Cav1.3钙离子通道蛋白的年龄相关性表达下调与老年性耳聋的研究
目的:
研究Cav1.3钙离子通道蛋白在老年性耳聋小鼠耳蜗组织中的表达，探讨其在老年性耳聋发病中的作用。
方法:
培育4w,14w,24w,48w不同年龄段的C57/6J小鼠为实验对象，应用听性脑干反应（auditorybrainstemresponse，ABR）分别检测4、14、24、48周龄的C57BL/6小鼠的听力。免疫荧光方法观察Cav1.3在不同周龄小鼠内耳组织中的分布，采用免疫印迹技术（westernbloting，WB）检测Cav1.3蛋白在不同年龄小鼠内耳中表达。同时采用实时荧光定量PCR（Real-timeRT-PCR）检测其基因（CACNA1D）mRNA在内耳组织的年龄相关性表达。
结果:
Cav1.3主要分布在小鼠耳蜗内外毛细胞、螺旋神经节、螺旋韧带、血管纹、螺旋（板）缘细胞。14、24、48周龄小鼠与4周龄小鼠相比ABR反应阈值明显提高（p<0.05），48周龄C57小鼠同前三组小鼠相比，ABR反应阈值显著提高（p<0.01）。随着鼠龄的增长，Cav1.3表达含量逐渐减少（p<0.01）。
结论：老年性耳聋小鼠Cav1.3钙离子通道蛋白表达含量随年龄增长而减少，其功能的异常和缺失可能在老年性耳聋的发病中起一定的作用。
第三部分缝隙连蛋白26(Connexin26)在听觉功能中的作用及耳聋机制的研究
目的:
研究Connexin26在听觉功能以及内耳主动听觉机理中的作用，探讨Connexin26缺失引起耳聋的机制。
方法:
运用loxP-Cre技术敲除耳蜗DCs和OPCs上的缝隙连蛋白26(Cx26)的表达。由Cx26loxP/loxP转基因鼠和Prox1-CreERT2小鼠杂交培育缝隙连蛋白26选择性敲除小鼠（以下简称Cx26cKO小鼠）。分别检测野生型、杂合子以及纯合子不同基因型小鼠听性脑干反应（auditorybrainstemresponse，ABR）、微音器电位（CM）、畸变耳声发射（DPOAE）、内淋巴电位（EP）。免疫组织化学的方法检测Cx26、Cx30以及外毛细胞电能动性蛋白Prestin的表达。甲苯氨蓝染色观察不同基因型小鼠螺旋神经节差异。采用实时荧光定量PCR（Real-timeRT-PCR）检测Prestin在野生型和纯合子小鼠的表达。
结果:在缝隙连蛋白26选择性敲除小鼠耳蜗顶回、中回及底回的Deiters’细胞和外柱细胞上均没有Cx26的表达。Cx26在耳蜗其他组织如螺旋缘以及外侧壁的表达正常。而另外一种连接蛋白Cx30在耳蜗组织中的表达也正常。Cx26cKO小鼠有听力损失，听性脑干反应阈值增加以及DPOAE降低，但是微音器电位和内淋巴电位均正常。外毛细胞电能动性蛋白Prestin的表达也并无异常，内耳的毛细胞和螺旋神经节也未发现明显的损失和退变。
结论：耳蜗主动放大机理依赖于支持细胞的缝隙连接。缝隙连蛋白26功能的缺失可以减弱耳蜗放大器的功能从而引起听力的损失。
PART ONE Expression Patterns of Cav1.3calcium channels in the rat cochlea
Objective: To investigate the expression of Cav1.3calcium channels in the rat cochlea and study its role in auditory physiology and pathology.
Methods:The distribution of Cav1.3calcium channels in the rat cochlea was detected by immunohistochemistry. The expression of Cav1.3calcium channels was measured with western bloting (WB) and reverse transcription-polymerase chain reaction (RT-PCR).
Results:Immunohistochemistry revealed that Cav1.3calcium channels were localized in the outer hair cells (OHCs), inner hair cells (IHCs), limbus laminae spiralis, spiral ganglion cell, spiral ligament and stria vascularis. The results of RT-PCR and Western blotting demonstrated Cav1.3calcium channels had a tissue-specific expression pattern. Cavl.3mRNA and protein were intensively expressed in the basilar membrane and spiral ganglion while moderate level of Cavl.3was observed in spiral ligament and stria vascularis.
Conclusion:The study preliminary reveals the expression patterns of Cavl.3calcium channels in the rat cochlea, providing a theoretical basis for further research on the role of Cav1.3calcium channels in the periphery auditory system.
PART Two Downregulation of Cav1.3calcium channel expression in the cochlea is associated with Presbycusis in C57BL/6mice
Objective:To investigate the expression of Cav1.3calcium channel in C57BL/6mice cochlea and study its correlation with presbycusis.
Methods:Auditory function was measured with auditory brainstem response (ABR) in C57BL/6mice at4,14,24and48weeks. The expression of Cav1.3calcium channels was detected by immunofluorescence,Western Blotting and Real-time RT-PCR at various ages.
Results:Immunofluorescence photographs reveal that Cav1.3channels were mainly localized in the hair cell, spiral ganglion cell, spiral ligment, stria vascularis, spiral limbus. Comparing with4-week group, the ABR threshold of4-,24-, and48-week increased (p<0.05). The ABR threshold at48-week group was significantly higher than others (p<0.01). Along with age, the missing hair cells and spiral ganglion cells increased, stria vascularis and spiral ligament atrophied, the expression of Cav1.3channels was gradually decrease d(p<0.01).
Conclusion:The expression of Cav1.3channels decreased along with age. Dysfunction or missing of Cavl.3calcium channels may be related to presbycusis.
PART Three Contribution of connexin26to active cochlear amplification and underlying mechanisms for connexin26deficiency induced hearing loss
Objective:To investigate Connexin26hearing function and contribution to active cochlear amplification and deafness mechanisms underlying Cx26deficiency induced hearing loss.
Methods:We used loxP-Cre technique to delete Cx26expression in Deiter cells (DCs) and outer pillar cells (OPCs). The Cx26conditional knockout (cKO) mouse was generated by crossing Cx26loxP/loxP transgenic mice with a Proxl-CreERT2mouse line. Auditory function was measured with auditory brainstem response (ABR), DPOAE, CM and EP in Cx26cKO mice. The expression of Cx26, Cx30and Prestein were detected by immunofluorescence staining. Consecutive cochlear paraffin sections were stained with toluidine blue to account SG neuron. Prestin expression at the transcriptional level was measured by real-time RT-PCR.
Results:Cx26labeling was absent in DCs and OPCs in Cx26cKO mice. The deletion of Cx26is visible in all three apical, middle, and basal turns. Cx26labeling in other cochlear structures, including the spiral limbus (SLM) and the lateral wall, remained normal. Cx30, which is another predominant connexin isoform in the cochlea, also retained normal expression. Targeted-deletion of Cx26in DCs and OPCs induced hearing loss The ABR threshold in homozygous mice was increased significantly and DPOAE was significantly reduced. CM and EP in Cx26cKO mice were normal. No reduction in prestin. No apparent cell degeneration in the Cx26cKO mouse cochlea.
Conclusion:The study demonstrates that active cochlear amplification in vivo is dependent on supporting cell gap junctions. These new findings also show that connexin26deficiency can reduce active cochlear amplification to induce hearing loss.
引文
Baig SM, Koschak A, Lieb A, et al.(2011) Loss of Ca(v)1.3(CACNA1D) function in a human channelopathy with bradycardia and congenital deafness. Nat Neurosci14:77-84.
Berridge MJ (1998) Neuronal calcium signaling. Neuron21:13-26.
Bosher SK, Warren RL (1978) Very low calcium content of cochlear endolymph, an extracellular fluid. Nature273:377-378
Brandt A, Striessnig J, Moser T (2003) Cav1.3channels are essential for development and presynaptic activity of cochlear inner hair cells. J Neurosci23:10832-10840.
Catterall WA (2000) Structure and regulation of voltage-gated Ca2+channels. Annu Rev Cell Dev Biol16:521-555.
Chen WC, Xue HZ, Hsu YL, Liu Q, Patel S, Davis RL (2011) Complex distribution patterns of voltage-gated calcium channel alpha-subunits in the spiral ganglion. Hear Res278:52-68.
Fettiplace R, Hackney CM (2006) The sensory and motor roles of auditory hair cells. Nature reviews. Neuroscience7:19-29.
Glowatzki E, Fuchs PA (2002) Transmitter release at the hair cell ribbon synapse. Nat Neurosci5:147-154
Glueckert R, Wietzorrek G, Kammen-Jolly K, Scholtz A, Stephan K, Striessnig J, Schrott-Fischer A (2003) Role of class D L-type Ca2+channels for cochlear morphology. Hear Res178:95-105.
Hafidi A, Dulon D (2004) Developmental expression of Ca(v)1.3(alphald) calcium channels in the mouse inner ear. Brain Res Dev Brain Res150:167-175.
Ikeda K, Kusakari J, Takasaka T, Saito Y (1987) The Ca2+activity of cochlear endolymph of the guinea pig and the effect of inhibitors. Hear Res26:117-125.
Inagaki A, Ugawa S, Yamamura H, Murakami S, Shimada S (2008) The CaV3.1T-type Ca2+channel contributes to voltage-dependent calcium currents in rat outer hair cells. Brain Res1201:68-77.
Inui T, Mori Y, Watanabe M, et al.(2007) Physiological role of L-type Ca2+channels in marginal cells in the stria vascularis of guinea pigs. J Physiol Sci57:287-298.
Lipscombe D, Helton TD, Xu W (2004) L-type calcium channels:the low down. J Neurophysiol92:2633-2641.
Mammano F, Bortolozzi M, Ortolano S, Anselmi F (2007) Ca2+signaling in the inner ear. Physiology (Bethesda)22:131-144.
Mangoni ME, Couette B, Bourinet E, Platzer J, Reimer D, Striessnig J, Nargeot J (2003) Functional role of L-type Cavl.3Ca2+channels in cardiac pacemaker activity. Proc Natl Acad Sci U S A100:5543-5548.
Michna M, Knirsch M, Hoda JC, et al.(2003) Cavl.3(alphalD) Ca2+currents in neonatal outer hair cells of mice. J Physiol553:747-758.
Mori Y, Watanabe M, Inui T, et al.(2009) Ca(2+) regulation of endocochlear potential in marginal cells. JPhysiol Sci59:355-365.
Moser T, Beutner D (2000) Kinetics of exocytosis and endocytosis at the cochlear inner hair cell afferent synapse of the mouse. Proc Natl Acad Sci U S A97:883-888
Nemzou NR, Bulankina AV, Khimich D, Giese A, Moser T (2006) Synaptic organization in cochlear inner hair cells deficient for the CaV1.3(alphalD) subunit of L-type Ca2+channels. Neuroscience141:1849-1860.
Ninoyu O, Meyer zum Gottesberge AM (1986) Changes in Ca++activity and DC potential in experimentally induced endolymphatic hydrops. Arch Otorhinolaryngol243:106-107
Ohmori H (1985) Mechano-electrical transduction currents in isolated vestibular hair cells of the chick. J Physiol359:189-217
Parsons TD, Lenzi D, Almers W, Roberts WM (1994) Calcium-triggered exocytosis and endocytosis in an isolated presynaptic cell:capacitance measurements in saccular hair cells. Neuron13:875-883.
Platzer J, Engel J, Schrott-Fischer A, et al.(2000) Congenital deafness and sinoatrial node dysfunction in mice lacking class D L-type Ca2+channels. Cell102:89-97.
Ricci AJ, Fettiplace R (1998) Calcium permeation of the turtle hair cell mechanotransducer channel and its relation to the composition of endolymph. J Physiol506(Pt1):159-173
Salt AN, Inamura N, Thalmann R, Vora A (1989) Calcium gradients in inner ear endolymph. Am J Otolaryngol10:371-375
Tanaka Y, Asanuma A, Yanagisawa K (1980) Potentials of outer hair cells and their membrane properties in cationic environments. Hear Res2:431-438
Zampini V, Johnson SL, Franz C, et al.(2010Pt1) Elementary properties of CaV1.3Ca(2+) channels expressed in mouse cochlear inner hair cells. J Physiol588:187-199.
Zuccotti A, Clementi S, Reinbothe T, Torrente A, Vandael DH, Pirone A (2011) Structural and functional differences between L-type calcium channels:crucial issues for future selective targeting. Trends Pharmacol Sci32:366-375.
Berridge MJ (1998) Neuronal calcium signaling. Neuron21:13-26.
Bezprozvanny IB (2010) Calcium signaling and neurodegeneration. Acta naturae2:72-82
Brandt A, Striessnig J, Moser T (2003) CaV1.3channels are essential for development and presynaptic activity of cochlear inner hair cells. J Neurosci23:10832-10840.
Brookes GB (1983) Vitamin D deficiency--a new cause of cochlear deafness. J Laryngol Otol97:405-420
Catterall WA (2000) Structure and regulation of voltage-gated Ca2+channels. Annu Rev Cell Dev Biol16:521-555.
Chen J, Chu H, Xiong H, et al.(2012) Expression patterns of CaV1.3channels in the rat cochlea. Acta Biochim Biophys Sin44:513-518.
Chen J, Chu H, Xiong H, et al.(2013) Downregulation of Cavl.3calcium channel expression in the cochlea is associated with age-related hearing loss in C57BL/6J mice. Neuroreport24:313-317.
Frisina RD (2009) Age-related hearing loss:ear and brain mechanisms. Annals of the New York Academy of Sciences1170:708-717.
Gibbons SJ, Brorson JR, Bleakman D, Chard PS, Miller RJ (1993) Calcium influx and neurodegeneration. Annals of the New York Academy of Sciences679:22-33
Glueckert R, Wietzorrek G, Kammen-Jolly K, Scholtz A, Stephan K, Striessnig J, Schrott-Fischer A (2003) Role of class D L-type Ca2+channels for cochlear morphology. Hear Res178:95-105.
Gratton MA, Vazquez AE (2003) Age-related hearing loss:current research. Current opinion in otolaryngology&head and neck surgery11:367-371
Hafidi A, Dulon D (2004) Developmental expression of Ca(v)1.3(alphald) calcium channels in the mouse inner ear. Brain Res Dev Brain Res150:167-175.
Han C, Someya S (2013) Mouse models of age-related mitochondrial neurosensory hearing loss. Molecular and cellular neurosciences55:95-100.
Huang Q, Tang J (2010) Age-related hearing loss or presbycusis. Eur Arch Otorhinolaryngol267:1179-1191.
Huang T (2007) Age-related hearing loss. Minnesota medicine90:48-50
Inagaki A, Ugawa S, Yamamura H, Murakami S, Shimada S (2008) The CaV3.1T-type Ca2+channel contributes to voltage-dependent calcium currents in rat outer hair cells. Brain Res1201:68-77.
Inui T, Mori Y, Watanabe M, et al.(2007) Physiological role of L-type Ca2+channels in marginal cells in the stria vascularis of guinea pigs. J Physiol Sci57:287-298.
Johnson KR, Zheng QY (2002) Ahl2, a second locus affecting age-related hearing loss in mice. Genomics80:461-464.
Johnson SL, Marcotti W (2008) Biophysical properties of CaV1.3calcium channels in gerbil inner hair cells. J Physiol586:1029-1042.
Knirsch M, Brandt N, Braig C, et al.(2007) Persistence of Ca(v)1.3Ca2+channels in mature outer hair cells supports outer hair cell afferent signaling. The Journal of neuroscience:the official journal of the Society for Neuroscience27:6442-6451doi:10.1523/JNEUROSCI.5364-06.2007
Kollmar R, Montgomery LG, Fak J, Henry LJ, Hudspeth AJ (1997) Predominance of the alphalD subunit in L-type voltage-gated Ca2+channels of hair cells in the chicken's cochlea. Proc Natl Acad Sci U S A94:14883-14888
Kurniawan C, Westendorp RG, de Craen AJ, Gussekloo J, de Laat J, van Exel E (2012) Gene dose of apolipoprotein E and age-related hearing loss. Neurobiology of aging33:2230-2237.
Li-Korotky HS (2012) Age-related hearing loss:quality of care for quality of life. The Gerontologist52:265-271.
Lipscombe D, Helton TD, Xu W (2004) L-type calcium channels:the low down. J Neurophysiol92:2633-2641.
Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the2(-Delta Delta C(T)) Method. Methods25:402-408.
Mammano F, Bortolozzi M, Ortolano S, Anselmi F (2007) Ca2+signaling in the inner ear. Physiology (Bethesda)22:131-144.
Mangoni ME, Couette B, Bourinet E, Platzer J, Reimer D, Striessnig J, Nargeot J (2003) Functional role of L-type Cavl.3Ca2+channels in cardiac pacemaker activity. Proc Natl Acad Sci U S A100:5543-5548.
Marambaud P, Dreses-Werringloer U, Vingtdeux V (2009) Calcium signaling in neurodegeneration. Molecular neurodegeneration4:20.
Menardo J, Tang Y, Ladrech S, et al.(2012) Oxidative stress, inflammation, and autophagic stress as the key mechanisms of premature age-related hearing loss in SAMP8mouse Cochlea. Antioxidants&redox signaling16:263-274.
Michna M, Knirsch M, Hoda JC, et al.(2003) Cavl.3(alphalD) Ca2+currents in neonatal outer hair cells of mice. J Physiol553:747-758.
Mori Y, Watanabe M, Inui T, et al.(2009) Ca(2+) regulation of endocochlear potential in marginal cells. JPhysiol Sci59:355-365.
Nemzou NR, Bulankina AV, Khimich D, Giese A, Moser T (2006) Synaptic organization in cochlear inner hair cells deficient for the CaV1.3(alphalD) subunit of L-type Ca2+channels. Neuroscience141:1849-1860.
Seidman MD, Ahmad N, Bai U (2002) Molecular mechanisms of age-related hearing loss. Ageing research reviews1:331-343
Seidman MD, Ahmad N, Joshi D, Seidman J, Thawani S, Quirk WS (2004) Age-related hearing loss and its association with reactive oxygen species and mitochondrial DNA damage. Acta oto-laryngologica. Supplementum:16-24
Seidman MD, Khan MJ, Bai U, Shirwany N, Quirk WS (2000) Biologic activity of mitochondrial metabolites on aging and age-related hearing loss. The American j ournal of otology21:161-167
Sharashenidze N, Schacht J, Kevanishvili Z (2007) Age-related hearing loss:gender differences. Georgian medical news:14-18
Smaili S, Hirata H, Ureshino R, et al.(2009) Calcium and cell death signaling in neurodegeneration and aging. Anais da Academia Brasileira de Ciencias81:467-475
Someya S, Prolla TA (2010) Mitochondrial oxidative damage and apoptosis in age-related hearing loss. Mechanisms of ageing and development131:480-486.
Wood JD, Muchinsky SJ, Filoteo AG, Penniston JT, Temp el BL (2004) Low endolymph calcium concentrations in deafwaddler2J mice suggest that PMCA2contributes to endolymph calcium maintenance. J Assoc Res Otolaryngol5:99-110.
Xiong H, Chu H, Zhou X, et al.(2011) Simultaneously reduced NKCC1and Na,K-ATPase expression in murine cochlear lateral wall contribute to conservation of endocochlear potential following a sensorineural hearing loss. Neurosci Lett488:204-209.
Zampini V, Johnson SL, Franz C, et al.(2010) Elementary properties of CaV1.3Ca(2+) channels expressed in mouse cochlear inner hair cells. J Physiol588:187-199.
Zhu X, Vasilyeva ON, Kim S, et al.(2007) Auditory efferent feedback system deficits precede age-related hearing loss:contralateral suppression of otoacoustic emissions in mice. The Journal of comparative neurology503:593-604.
Zundorf G, Reiser G (2011) Calcium dysregulation and homeostasis of neural calcium in the molecular mechanisms of neurodegenerative diseases provide multiple targets for neuroprotection. Antioxidants&redox signaling14:1275-1288.
Ashmore J (2008) Cochlear outer hair cell motility. Physiological reviews88:173-210.
Bermingham-McDonogh O, Oesterle EC, Stone JS, Hume CR, Huynh HM, Hayashi T (2006) Expression of Proxl during mouse cochlear development. The Journal of comparative neurology496:172-186.
Bobbin RP (2001) ATP-induced movement of the stalks of isolated cochlear Deiters' cells. Neuroreport12:2923-2926
Brownell WE, Bader CR, Bertrand D, de Ribaupierre Y (1985) Evoked mechanical responses of isolated cochlear outer hair cells. Science227:194-196
Castillo FJ, Castillo Ⅰ (2011) The DFNB1subtype of autosomal recessive non-syndromic hearing impairment. Frontiers in bioscience:a journal and virtual library16:3252-3274
Chan DK, Hudspeth AJ (2005) Ca2+current-driven nonlinear amplification by the mammalian cochlea in vitro. Nature neuroscience8:149-155.
Chen J, Zhu Y, Parsa A, Liang C, Zong L, Kalinec F, Zhao H-B (2013) New function for Connexin26(Cx26) in the cochlea and new mechanism for deafness induced by deficiency in Cx26. The36th Assoc. Res. Otolaryngol. Annual Meeting. Baltimore, MD. http://www.aro.org (2013).
Cohen-Salmon M, Ott T, Michel V, et al.(2002) Targeted ablation of connexin26in the inner ear epithelial gap junction network causes hearing impairment and cell death. Current biology:CB12:1106-1111
Dallos P (2008) Cochlear amplification, outer hair cells and prestin. Current opinion in neurobiology18:370-376.
Dallos P, Corey ME (1991) The role of outer hair cell motility in cochlear tuning. Current opinion in neurobiology1:215-220
Dallos P, Wu X, Cheatham MA, et al.(2008) Prestin-based outer hair cell motility is necessary for mammalian cochlear amplification. Neuron58:333-339.
Dulon D, Blanchet C, Laffon E (1994) Photo-released intracellular Ca2+evokes reversible mechanical responses in supporting cells of the guinea-pig organ of Corti. Biochemical and biophysical research communications201:1263-1269.
Engel-Yeger B, Zaaroura S, Zlotogora J, et al.(2002) The effects of a connexin26mutation--35delG--on oto-acoustic emissions and brainstem evoked potentials: homozygotes and carriers. Hearing research163:93-100
Engel-Yeger B, Zaaroura S, Zlotogora J, et al.(2003) Otoacoustic emissions and brainstem evoked potentials in compound carriers of connexin26mutations. Hearing research175:140-151
Fettiplace R (2006) Active hair bundle movements in auditory hair cells. The Journal of physiology576:29-36.
Flock A, Flock B, Fridberger A, Scarfone E, Ulfendahl M (1999) Supporting cells contribute to control of hearing sensitivity. The Journal of neuroscience:the official journal of the Society for Neuroscience19:4498-4507
Forge A, Becker D, Casalotti S, Edwards J, Marziano N, Nevill G (2003) Gap junctions in the inner ear:comparison of distribution patterns in different vertebrates and assessement of connexin composition in mammals. The Journal of comparative neurology467:207-231.
Fridberger A, Flock A, Ulfendahl M, Flock B (1998) Acoustic overstimulation increases outer hair cell Ca2+concentrations and causes dynamic contractions of the hearing organ. Proceedings of the National Academy of Sciences of the United States of America95:7127-7132
Hudspeth AJ (2008) Making an effort to listen:mechanical amplification in the ear. Neuron59:530-545.
Iwasa KH (1993) Effect of stress on the membrane capacitance of the auditory outer hair cell. Biophysical journal65:492-498.
Kakehata S, Santos-Sacchi J (1995) Membrane tension directly shifts voltage dependence of outer hair cell motility and associated gating charge. Biophysical journal68:2190-2197.
Kelsell DP, Dunlop J, Stevens HP, et al.(1997) Connexin26mutations in hereditary non-syndromic sensorineural deafness. Nature387:80-83.
Kennedy HJ, Crawford AC, Fettiplace R (2005) Force generation by mammalian hair bundles supports a role in cochlear amplification. Nature433:880-883.
Kikuchi T, Kimura RS, Paul DL, Adams JC (1995) Gap junctions in the rat cochlea: immunohistochemical and ultrastructural analysis. Anatomy and embryology191:101-118
Kirjavainen A, Sulg M, Heyd F, et al.(2008) Proxl interacts with Atohl and Gfil, and regulates cellular differentiation in the inner ear sensory epithelia. Developmental biology322:33-45.
Liang C, Zhu Y, Zong L, Lu GJ, Zhao HB (2012) Cell degeneration is not a primary causer for Connexin26(GJB2) deficiency associated hearing loss. Neuroscience letters528:36-41.
Liberman MC, Gao J, He DZ, Wu X, Jia S, Zuo J (2002) Prestin is required for electromotility of the outer hair cell and for the cochlear amplifier. Nature419:300-304.
Mistrik P, Ashmore JF (2010) Reduced electromotility of outer hair cells associated with connexin-related forms of deafness:an in silico study of a cochlear network mechanism. Journal of the Association for Research in Otolaryngology:JARO11:559-571.
Parsa A, Webster P, Kalinec F (2012) Deiters cells tread a narrow path--the Deiters cells-basilar membrane junction. Hearing research290:13-20.
Rajagopalan L, Greeson JN, Xia A, et al.(2007) Tuning of the outer hair cell motor by membrane cholesterol. The Journal of biological chemistry282:36659-36670.
Srinivasan RS, Dillard ME, Lagutin OV, et al.(2007) Lineage tracing demonstrates the venous origin of the mammalian lymphatic vasculature. Genes&development21:2422-2432.
Wang Y, Chang Q, Tang W, Sun Y, Zhou B, Li H, Lin X (2009) Targeted connexin26ablation arrests postnatal development of the organ of Corti. Biochemical and biophysical research communications385:33-37.
Yu N, Zhao HB (2009) Modulation of outer hair cell electromotility by cochlear supporting cells and gap junctions. PloS one4:e7923
Yu N, Zhu ML, Johnson B, Liu YP, Jones RO, Zhao HB (2008) Prestin up-regulation in chronic salicylate (aspirin) administration:an implication of functional dependence of prestin expression. Cellular and molecular life sciences:CMLS65:2407-2418.
Yu Y, Weber T, Yamashita T, Liu Z, Valentine MB, Cox BC, Zuo J (2010) In vivo proliferation of postmitotic cochlear supporting cells by acute ablation of the retinoblastoma protein in neonatal mice. The Journal of neuroscience:the official journal of the Society for Neuroscience30:5927-5936.
Zhao HB (2000) Directional rectification of gap junctional voltage gating between dieters cells in the inner ear of guinea pig. Neuroscience letters296:105-108
Zhao HB, Kikuchi T, Ngezahayo A, White TW (2006) Gap junctions and cochlear homeostasis. The Journal of membrane biology209:177-186.
Zhao HB, Santos-Sacchi J (1999) Auditory collusion and a coupled couple of outer hair cells. Nature399:359-362.
Zhao HB, Yu N (2006) Distinct and gradient distributions of connexin26and connexin30in the cochlear sensory epithelium of guinea pigs. The Journal of comparative neurology499:506-518.
Zheng J, Shen W, He DZ, Long KB, Madison LD, Dallos P (2000) Prestin is the motor protein of cochlear outer hair cells. Nature405:149-155.
Zhu Y, Zhao HB (2010) ATP-mediated potassium recycling in the cochlear supporting cells. Purinergic signalling6:221-229
Zhu Y, Liang C, Chen J, Zong L, Chen GD, Zhao HB.Active cochlear amplification is dependent on supporting cell gap junctions. Nat. Commun.4:1786doi:10.1038/ncomms2806(2013).
Ballinger SW, Shoffner JM, Hedaya EV, Trounce I, Polak MA, Koontz DA, Wallace DC (1992) Maternally transmitted diabetes and deafness associated with a10.4kb mitochondrial DNA deletion. Nature genetics1:11-15
Byers T, Bowman B (1993) Vitamin E supplements and coronary heart disease. Nutrition reviews51:333-336
Choi BH (1993) Oxygen, antioxidants and brain dysfunction. Yonsei medical journal 34:1-10
Davis RR, Newlander JK, Ling X, Cortopassi GA, Krieg EF, Erway LC (2001) Genetic basis for susceptibility to noise-induced hearing loss in mice. Hearing research155:82-90
DiMauro S, Bonilla E, Lombes A, Shanske S, Minetti C, Moraes CT (1990) Mitochondrial encephalomyopathies. Neurologic clinics8:483-506
Frolenkov GI (2006) Regulation of electromotility in the cochlear outer hair cell. The Journal of physiology576:43-48.
Gerbitz KD, Obermaier-Kusser B, Lestienne P, et al.(1990) Mutations of the mitochondrial DNA: the contribution of DNA techniques to the diagnosis of mitochondrial encephalomyopathies. Journal of clinical chemistry and clinical biochemistry. Zeitschrift for klinische Chemie und klinische Biochemie28:241-250
Gold M, Rapin I, Shanske S (1991) Mitochondrial inheritance of acquired deafness. Annals of the New York Academy of Sciences630:301-302
Grimes AM, Grady CL, Foster NL, Sunderland T, Patronas NJ (1985) Central auditory function in Alzheimer's disease. Neurology35:352-358
Grossman LI (1990) Mitochondrial DNA in sickness and in health. American journal of human genetics46:415-417
Halliwell B (1994) Free radicals and antioxidants:a personal view. Nutrition reviews52:253-265
Hiyama K, Hirai Y, Kyoizumi S, et al.(1995) Activation of telomerase in human lymphocytes and hematopoietic progenitor cells. Journal of immunology155:3711-3715
Hockenbery DM, Oltvai ZN, Yin XM, Milliman CL, Korsmeyer SJ (1993) Bcl-2functions in an antioxidant pathway to prevent apoptosis. Cell75:241-251
Huang T (2007) Age-related hearing loss. Minnesota medicine90:48-50
Ikeda K, Sunose H, Takase T. Effects of free radicals on in tracellular calcium concentration in the isolated outer hair cell of the guinea pig cochlea. Acta Ot olaryngol,1993;115:137
Johnson KR, Erway LC, Cook SA, Willott JF, Zheng QY (1997) A major gene affecting age-related hearing loss in C57BL/6J mice. Hearing research114:83-92
Kane DJ, Sarafian TA, Anton R, et al.(1993) Bcl-2inhibition of neural death:decreased generation of reactive oxygen species. Science262:1274-1277.
Lin MJ, Su MC, Tan CT, et al. The efect of larginine on slow motility of malnmalian outer hair cell. Hear Res,2003,178:52-58
Lyras L, Cairns NJ, Jenner A, Jenner P, Halliwell B (1997) An assessment of oxidative damage to proteins, lipids, and DNA in brain from patients with Alzheimer's disease. Journal of neurochemistry68:2061-2069
Miyabayashi S, Hanamizu H, Endo H, Tada K, Horai S (1991) A new type of mitochondrial DNA deletion in patients with encephalomyopathy. Journal of inherited metabolic disease14:805-812
Moon H, Baek D, Lee B, et al.(2002) Soybean ascorbate peroxidase suppresses Bax-induced apoptosis in yeast by inhibiting oxygen radical generation. Biochemical and biophysical research communications290:457-462.
Nagley P, Mackay IR, Baumer A, et al.(1992) Mitochondrial DNA mutation associated with aging and degenerative disease. Annals of the New York Academy of Sciences673:92-102
Nakashima T, Naganawa S. Disorders of cochlear blood flow. Brain Res Brain Res Rev.2003;43(1):17-28
Oliver D, He DZ, Klocker N, et al.(2001) Intracellular anions as the voltage sensor of prestin, the outer hair cell motor protein. Science292:2340-2343.
Olrvai ZN, Milliman CL, Korsmeyer SJ (1993) Bcl-2heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell74:609-619
Ospeck M, Dong XX, lwasa KH. Limiting frequency of the cochlear amplifier based on electromotility of outer hair cells. Biophys J,2003,84(2pt1):739-749
Pommier JP, Lebeau J, Ducray C, Sabatier L (1995) Chromosomal instability and alteration of telomere repeat sequences. Biochimie77:817-825
Prazma J, Carrasco VN, Butler B, Waters G, Anderson T, Pillsbury HC (1990) Cochlear microcirculation in young and old gerbils. Archives of otolaryngology-head&neck surgery116:932-936
Sawada S, Takeda T, Kakigi A, Saito H, Suehiro T, Nakauchi Y, Chikamori K (1997) Audiological findings of sensorineural deafness associated with a mutation in the mitochondrial DNA. The American journal of otology18:332-335
Seidman MD, Ahmad N, Bai U (2002) Molecular mechanisms of age-related hearing loss. Ageing research reviews1:331-343
Seidman MD, Khan MJ, Dolan DF, Quirk WS (1996) Age-related differences in cochlear microcirculation and auditory brain stem response. Archives of otolaryngology--head&neck surgery122:1221-1226
Seidman MD, Shivapuja BG, Quirk WS (1993) The protective effects of allopurinol and superoxide dismutase on noise-induced cochlear damage. Otolaryngology-head and neck surgery:official journal of American Academy of Otolaryngology-Head and Neck Surgery109:1052-1056
Serratrice G, Desnuelle C (1990)[Mitochondrial encephalomyopathies]. Presse medicale19:645-647
Sheehan JP, Swerdlow RH, Miller SW, Davis RE, Parks JK, Parker WD, Tuttle JB (1997) Calcium homeostasis and reactive oxygen species production in cells transformed by mitochondria from individuals with sporadic Alzheimer's disease. The Journal of neuroscience:the official journal of the Society for Neuroscience17:4612-4622
Simpson GV, Knight RT, Brailowsky S, Prospero-Garcia O, Scabini D (1985) Altered peripheral and brainstem auditory function in aged rats. Brain research348:28-35
Smith MA, Perry G (1995) Free radical damage, iron, and Alzheimer's disease. Journal of the neurological sciences134Suppl:92-94
Staecker H, Zheng QY, Van De Water TR (2001) Oxidative stress in aging in the C57B16/J mouse cochlea. Acta oto-laryngologica121:666-672
Strehler BL (1985) Aging:a challenge to science, society, and the individual. Clinics in geriatric medicine1:5-13
van den Ouweland JM, Lemkes HH, Ruitenbeek W, et al.(1992) Mutation in mitochondrial tRNA(Leu)(UUR) gene in a large pedigree with maternally transmitted type Ⅱ diabetes mellitus and deafness. Nature genetics1:368-371
Wallace DC (1997) Mitochondrial DNA in aging and disease. Scientific American277:40-47
Zenner K, Gold R, Meurers B, Reichmann H (1990)[Mitochondrial encephalomyopathies. A comparison of Kearns-Sayre syndrome, MELAS and MERRF]. Der Nervenarzt61:597-603
陈金(2010)Cav1.3钙离子通道蛋白在内耳的表达和年龄相关性听力损失的研究[D].华中科技大学(硕士论文)
Berridge MJ (1998) Neuronal calcium signaling. Neuron21:13-26.
Bosher SK, Warren RL (1978) Very low calcium content of cochlear endolymph, an extracellular fluid. Nature273:377-378
Brandt A, Striessnig J, Moser T (2003) Cav1.3channels are essential for development and presynaptic activity of cochlear inner hair cells. J Neurosci23:10832-10840.
Catterall WA (2000) Structure and regulation of voltage-gated Ca2+channels. Annu Rev Cell Dev Biol16:521-555.
Chen WC, Xue HZ, Hsu YL, Liu Q, Patel S, Davis RL (2011) Complex distribution patterns of voltage-gated calcium channel alpha-subunits in the spiral ganglion. Hear Res278:52-68.
Fettiplace R, Hackney CM (2006) The sensory and motor roles of auditory hair cells. Nature reviews. Neuroscience7:19-29.
Glowatzki E, Fuchs PA (2002) Transmitter release at the hair cell ribbon synapse. Nat Neurosci5:147-154
Glueckert R, Wietzorrek G, Kammen-Jolly K, Scholtz A, Stephan K, Striessnig J, Schrott-Fischer A (2003) Role of class D L-type Ca2+channels for cochlear morphology. Hear Res178:95-105.
Hafidi A, Dulon D (2004) Developmental expression of Ca(v)1.3(alphald) calcium channels in the mouse inner ear. Brain Res Dev Brain Res150:167-175.
Ikeda K, Kusakari J, Takasaka T, Saito Y (1987) The Ca2+activity of cochlear endolymph of the guinea pig and the effect of inhibitors. Hear Res26:117-125.
Inagaki A, Ugawa S, Yamamura H, Murakami S, Shimada S (2008) The CaV3.1T-type Ca2+channel contributes to voltage-dependent calcium currents in rat outer hair cells. Brain Res1201:68-77.
Inui T, Mori Y, Watanabe M, et al.(2007) Physiological role of L-type Ca2+channels in marginal cells in the stria vascularis of guinea pigs. J Physiol Sci57:287-298.
Lipscombe D, Helton TD, Xu W (2004) L-type calcium channels:the low down. J Neurophysiol92:2633-2641.
Mammano F, Bortolozzi M, Ortolano S, Anselmi F (2007) Ca2+signaling in the inner ear. Physiology (Bethesda)22:131-144.
Mangoni ME, Couette B, Bourinet E, Platzer J, Reimer D, Striessnig J, Nargeot J (2003) Functional role of L-type Cavl.3Ca2+channels in cardiac pacemaker activity. Proc Natl Acad Sci U S A100:5543-5548.
Michna M, Knirsch M, Hoda JC, et al.(2003) Cavl.3(alphalD) Ca2+currents in neonatal outer hair cells of mice. J Physiol553:747-758.
Mori Y, Watanabe M, Inui T, et al.(2009) Ca(2+) regulation of endocochlear potential in marginal cells. JPhysiol Sci59:355-365.
Moser T, Beutner D (2000) Kinetics of exocytosis and endocytosis at the cochlear inner hair cell afferent synapse of the mouse. Proc Natl Acad Sci U S A97:883-888
Nemzou NR, Bulankina AV, Khimich D, Giese A, Moser T (2006) Synaptic organization in cochlear inner hair cells deficient for the CaV1.3(alphalD) subunit of L-type Ca2+channels. Neuroscience141:1849-1860.
Ninoyu O, Meyer zum Gottesberge AM (1986) Changes in Ca++activity and DC potential in experimentally induced endolymphatic hydrops. Arch Otorhinolaryngol243:106-107
Ohmori H (1985) Mechano-electrical transduction currents in isolated vestibular hair cells of the chick. J Physiol359:189-217
Parsons TD, Lenzi D, Almers W, Roberts WM (1994) Calcium-triggered exocytosis and endocytosis in an isolated presynaptic cell:capacitance measurements in saccular hair cells. Neuron13:875-883.
Platzer J, Engel J, Schrott-Fischer A, et al.(2000) Congenital deafness and sinoatrial node dysfunction in mice lacking class D L-type Ca2+channels. Cell102:89-97.
Ricci AJ, Fettiplace R (1998) Calcium permeation of the turtle hair cell mechanotransducer channel and its relation to the composition of endolymph. J Physiol506(Pt1):159-173
Salt AN, Inamura N, Thalmann R, Vora A (1989) Calcium gradients in inner ear endolymph. Am J Otolaryngol10:371-375
Tanaka Y, Asanuma A, Yanagisawa K (1980) Potentials of outer hair cells and their membrane properties in cationic environments. Hear Res2:431-438
Zampini V, Johnson SL, Franz C, et al.(2010Pt1) Elementary properties of CaV1.3Ca(2+) channels expressed in mouse cochlear inner hair cells. J Physiol588:187-199.
Zuccotti A, Clementi S, Reinbothe T, Torrente A, Vandael DH, Pirone A (2011) Structural and functional differences between L-type calcium channels:crucial issues for future selective targeting. Trends Pharmacol Sci32:366-375.
Berridge MJ (1998) Neuronal calcium signaling. Neuron21:13-26.
Bezprozvanny IB (2010) Calcium signaling and neurodegeneration. Acta naturae2:72-82
Brandt A, Striessnig J, Moser T (2003) CaV1.3channels are essential for development and presynaptic activity of cochlear inner hair cells. J Neurosci23:10832-10840.
Brookes GB (1983) Vitamin D deficiency--a new cause of cochlear deafness. J Laryngol Otol97:405-420
Catterall WA (2000) Structure and regulation of voltage-gated Ca2+channels. Annu Rev Cell Dev Biol16:521-555.
Chen J, Chu H, Xiong H, et al.(2012) Expression patterns of CaV1.3channels in the rat cochlea. Acta Biochim Biophys Sin44:513-518.
Chen J, Chu H, Xiong H, et al.(2013) Downregulation of Cavl.3calcium channel expression in the cochlea is associated with age-related hearing loss in C57BL/6J mice. Neuroreport24:313-317.
Frisina RD (2009) Age-related hearing loss:ear and brain mechanisms. Annals of the New York Academy of Sciences1170:708-717.
Gibbons SJ, Brorson JR, Bleakman D, Chard PS, Miller RJ (1993) Calcium influx and neurodegeneration. Annals of the New York Academy of Sciences679:22-33
Glueckert R, Wietzorrek G, Kammen-Jolly K, Scholtz A, Stephan K, Striessnig J, Schrott-Fischer A (2003) Role of class D L-type Ca2+channels for cochlear morphology. Hear Res178:95-105.
Gratton MA, Vazquez AE (2003) Age-related hearing loss:current research. Current opinion in otolaryngology&head and neck surgery11:367-371
Hafidi A, Dulon D (2004) Developmental expression of Ca(v)1.3(alphald) calcium channels in the mouse inner ear. Brain Res Dev Brain Res150:167-175.
Han C, Someya S (2013) Mouse models of age-related mitochondrial neurosensory hearing loss. Molecular and cellular neurosciences55:95-100.
Huang Q, Tang J (2010) Age-related hearing loss or presbycusis. Eur Arch Otorhinolaryngol267:1179-1191.
Huang T (2007) Age-related hearing loss. Minnesota medicine90:48-50
Inagaki A, Ugawa S, Yamamura H, Murakami S, Shimada S (2008) The CaV3.1T-type Ca2+channel contributes to voltage-dependent calcium currents in rat outer hair cells. Brain Res1201:68-77.
Inui T, Mori Y, Watanabe M, et al.(2007) Physiological role of L-type Ca2+channels in marginal cells in the stria vascularis of guinea pigs. J Physiol Sci57:287-298.
Johnson KR, Zheng QY (2002) Ahl2, a second locus affecting age-related hearing loss in mice. Genomics80:461-464.
Johnson SL, Marcotti W (2008) Biophysical properties of CaV1.3calcium channels in gerbil inner hair cells. J Physiol586:1029-1042.
Knirsch M, Brandt N, Braig C, et al.(2007) Persistence of Ca(v)1.3Ca2+channels in mature outer hair cells supports outer hair cell afferent signaling. The Journal of neuroscience:the official journal of the Society for Neuroscience27:6442-6451doi:10.1523/JNEUROSCI.5364-06.2007
Kollmar R, Montgomery LG, Fak J, Henry LJ, Hudspeth AJ (1997) Predominance of the alphalD subunit in L-type voltage-gated Ca2+channels of hair cells in the chicken's cochlea. Proc Natl Acad Sci U S A94:14883-14888
Kurniawan C, Westendorp RG, de Craen AJ, Gussekloo J, de Laat J, van Exel E (2012) Gene dose of apolipoprotein E and age-related hearing loss. Neurobiology of aging33:2230-2237.
Li-Korotky HS (2012) Age-related hearing loss:quality of care for quality of life. The Gerontologist52:265-271.
Lipscombe D, Helton TD, Xu W (2004) L-type calcium channels:the low down. J Neurophysiol92:2633-2641.
Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the2(-Delta Delta C(T)) Method. Methods25:402-408.
Mammano F, Bortolozzi M, Ortolano S, Anselmi F (2007) Ca2+signaling in the inner ear. Physiology (Bethesda)22:131-144.
Mangoni ME, Couette B, Bourinet E, Platzer J, Reimer D, Striessnig J, Nargeot J (2003) Functional role of L-type Cavl.3Ca2+channels in cardiac pacemaker activity. Proc Natl Acad Sci U S A100:5543-5548.
Marambaud P, Dreses-Werringloer U, Vingtdeux V (2009) Calcium signaling in neurodegeneration. Molecular neurodegeneration4:20.
Menardo J, Tang Y, Ladrech S, et al.(2012) Oxidative stress, inflammation, and autophagic stress as the key mechanisms of premature age-related hearing loss in SAMP8mouse Cochlea. Antioxidants&redox signaling16:263-274.
Michna M, Knirsch M, Hoda JC, et al.(2003) Cavl.3(alphalD) Ca2+currents in neonatal outer hair cells of mice. J Physiol553:747-758.
Mori Y, Watanabe M, Inui T, et al.(2009) Ca(2+) regulation of endocochlear potential in marginal cells. JPhysiol Sci59:355-365.
Nemzou NR, Bulankina AV, Khimich D, Giese A, Moser T (2006) Synaptic organization in cochlear inner hair cells deficient for the CaV1.3(alphalD) subunit of L-type Ca2+channels. Neuroscience141:1849-1860.
Seidman MD, Ahmad N, Bai U (2002) Molecular mechanisms of age-related hearing loss. Ageing research reviews1:331-343
Seidman MD, Ahmad N, Joshi D, Seidman J, Thawani S, Quirk WS (2004) Age-related hearing loss and its association with reactive oxygen species and mitochondrial DNA damage. Acta oto-laryngologica. Supplementum:16-24
Seidman MD, Khan MJ, Bai U, Shirwany N, Quirk WS (2000) Biologic activity of mitochondrial metabolites on aging and age-related hearing loss. The American j ournal of otology21:161-167
Sharashenidze N, Schacht J, Kevanishvili Z (2007) Age-related hearing loss:gender differences. Georgian medical news:14-18
Smaili S, Hirata H, Ureshino R, et al.(2009) Calcium and cell death signaling in neurodegeneration and aging. Anais da Academia Brasileira de Ciencias81:467-475
Someya S, Prolla TA (2010) Mitochondrial oxidative damage and apoptosis in age-related hearing loss. Mechanisms of ageing and development131:480-486.
Wood JD, Muchinsky SJ, Filoteo AG, Penniston JT, Temp el BL (2004) Low endolymph calcium concentrations in deafwaddler2J mice suggest that PMCA2contributes to endolymph calcium maintenance. J Assoc Res Otolaryngol5:99-110.
Xiong H, Chu H, Zhou X, et al.(2011) Simultaneously reduced NKCC1and Na,K-ATPase expression in murine cochlear lateral wall contribute to conservation of endocochlear potential following a sensorineural hearing loss. Neurosci Lett488:204-209.
Zampini V, Johnson SL, Franz C, et al.(2010) Elementary properties of CaV1.3Ca(2+) channels expressed in mouse cochlear inner hair cells. J Physiol588:187-199.
Zhu X, Vasilyeva ON, Kim S, et al.(2007) Auditory efferent feedback system deficits precede age-related hearing loss:contralateral suppression of otoacoustic emissions in mice. The Journal of comparative neurology503:593-604.
Zundorf G, Reiser G (2011) Calcium dysregulation and homeostasis of neural calcium in the molecular mechanisms of neurodegenerative diseases provide multiple targets for neuroprotection. Antioxidants&redox signaling14:1275-1288.
Ashmore J (2008) Cochlear outer hair cell motility. Physiological reviews88:173-210.
Bermingham-McDonogh O, Oesterle EC, Stone JS, Hume CR, Huynh HM, Hayashi T (2006) Expression of Proxl during mouse cochlear development. The Journal of comparative neurology496:172-186.
Bobbin RP (2001) ATP-induced movement of the stalks of isolated cochlear Deiters' cells. Neuroreport12:2923-2926
Brownell WE, Bader CR, Bertrand D, de Ribaupierre Y (1985) Evoked mechanical responses of isolated cochlear outer hair cells. Science227:194-196
Castillo FJ, Castillo Ⅰ (2011) The DFNB1subtype of autosomal recessive non-syndromic hearing impairment. Frontiers in bioscience:a journal and virtual library16:3252-3274
Chan DK, Hudspeth AJ (2005) Ca2+current-driven nonlinear amplification by the mammalian cochlea in vitro. Nature neuroscience8:149-155.
Chen J, Zhu Y, Parsa A, Liang C, Zong L, Kalinec F, Zhao H-B (2013) New function for Connexin26(Cx26) in the cochlea and new mechanism for deafness induced by deficiency in Cx26. The36th Assoc. Res. Otolaryngol. Annual Meeting. Baltimore, MD. http://www.aro.org (2013).
Cohen-Salmon M, Ott T, Michel V, et al.(2002) Targeted ablation of connexin26in the inner ear epithelial gap junction network causes hearing impairment and cell death. Current biology:CB12:1106-1111
Dallos P (2008) Cochlear amplification, outer hair cells and prestin. Current opinion in neurobiology18:370-376.
Dallos P, Corey ME (1991) The role of outer hair cell motility in cochlear tuning. Current opinion in neurobiology1:215-220
Dallos P, Wu X, Cheatham MA, et al.(2008) Prestin-based outer hair cell motility is necessary for mammalian cochlear amplification. Neuron58:333-339.
Dulon D, Blanchet C, Laffon E (1994) Photo-released intracellular Ca2+evokes reversible mechanical responses in supporting cells of the guinea-pig organ of Corti. Biochemical and biophysical research communications201:1263-1269.
Engel-Yeger B, Zaaroura S, Zlotogora J, et al.(2002) The effects of a connexin26mutation--35delG--on oto-acoustic emissions and brainstem evoked potentials: homozygotes and carriers. Hearing research163:93-100
Engel-Yeger B, Zaaroura S, Zlotogora J, et al.(2003) Otoacoustic emissions and brainstem evoked potentials in compound carriers of connexin26mutations. Hearing research175:140-151
Fettiplace R (2006) Active hair bundle movements in auditory hair cells. The Journal of physiology576:29-36.
Flock A, Flock B, Fridberger A, Scarfone E, Ulfendahl M (1999) Supporting cells contribute to control of hearing sensitivity. The Journal of neuroscience:the official journal of the Society for Neuroscience19:4498-4507
Forge A, Becker D, Casalotti S, Edwards J, Marziano N, Nevill G (2003) Gap junctions in the inner ear:comparison of distribution patterns in different vertebrates and assessement of connexin composition in mammals. The Journal of comparative neurology467:207-231.
Fridberger A, Flock A, Ulfendahl M, Flock B (1998) Acoustic overstimulation increases outer hair cell Ca2+concentrations and causes dynamic contractions of the hearing organ. Proceedings of the National Academy of Sciences of the United States of America95:7127-7132
Hudspeth AJ (2008) Making an effort to listen:mechanical amplification in the ear. Neuron59:530-545.
Iwasa KH (1993) Effect of stress on the membrane capacitance of the auditory outer hair cell. Biophysical journal65:492-498.
Kakehata S, Santos-Sacchi J (1995) Membrane tension directly shifts voltage dependence of outer hair cell motility and associated gating charge. Biophysical journal68:2190-2197.
Kelsell DP, Dunlop J, Stevens HP, et al.(1997) Connexin26mutations in hereditary non-syndromic sensorineural deafness. Nature387:80-83.
Kennedy HJ, Crawford AC, Fettiplace R (2005) Force generation by mammalian hair bundles supports a role in cochlear amplification. Nature433:880-883.
Kikuchi T, Kimura RS, Paul DL, Adams JC (1995) Gap junctions in the rat cochlea: immunohistochemical and ultrastructural analysis. Anatomy and embryology191:101-118
Kirjavainen A, Sulg M, Heyd F, et al.(2008) Proxl interacts with Atohl and Gfil, and regulates cellular differentiation in the inner ear sensory epithelia. Developmental biology322:33-45.
Liang C, Zhu Y, Zong L, Lu GJ, Zhao HB (2012) Cell degeneration is not a primary causer for Connexin26(GJB2) deficiency associated hearing loss. Neuroscience letters528:36-41.
Liberman MC, Gao J, He DZ, Wu X, Jia S, Zuo J (2002) Prestin is required for electromotility of the outer hair cell and for the cochlear amplifier. Nature419:300-304.
Mistrik P, Ashmore JF (2010) Reduced electromotility of outer hair cells associated with connexin-related forms of deafness:an in silico study of a cochlear network mechanism. Journal of the Association for Research in Otolaryngology:JARO11:559-571.
Parsa A, Webster P, Kalinec F (2012) Deiters cells tread a narrow path--the Deiters cells-basilar membrane junction. Hearing research290:13-20.
Rajagopalan L, Greeson JN, Xia A, et al.(2007) Tuning of the outer hair cell motor by membrane cholesterol. The Journal of biological chemistry282:36659-36670.
Srinivasan RS, Dillard ME, Lagutin OV, et al.(2007) Lineage tracing demonstrates the venous origin of the mammalian lymphatic vasculature. Genes&development21:2422-2432.
Wang Y, Chang Q, Tang W, Sun Y, Zhou B, Li H, Lin X (2009) Targeted connexin26ablation arrests postnatal development of the organ of Corti. Biochemical and biophysical research communications385:33-37.
Yu N, Zhao HB (2009) Modulation of outer hair cell electromotility by cochlear supporting cells and gap junctions. PloS one4:e7923
Yu N, Zhu ML, Johnson B, Liu YP, Jones RO, Zhao HB (2008) Prestin up-regulation in chronic salicylate (aspirin) administration:an implication of functional dependence of prestin expression. Cellular and molecular life sciences:CMLS65:2407-2418.
Yu Y, Weber T, Yamashita T, Liu Z, Valentine MB, Cox BC, Zuo J (2010) In vivo proliferation of postmitotic cochlear supporting cells by acute ablation of the retinoblastoma protein in neonatal mice. The Journal of neuroscience:the official journal of the Society for Neuroscience30:5927-5936.
Zhao HB (2000) Directional rectification of gap junctional voltage gating between dieters cells in the inner ear of guinea pig. Neuroscience letters296:105-108
Zhao HB, Kikuchi T, Ngezahayo A, White TW (2006) Gap junctions and cochlear homeostasis. The Journal of membrane biology209:177-186.
Zhao HB, Santos-Sacchi J (1999) Auditory collusion and a coupled couple of outer hair cells. Nature399:359-362.
Zhao HB, Yu N (2006) Distinct and gradient distributions of connexin26and connexin30in the cochlear sensory epithelium of guinea pigs. The Journal of comparative neurology499:506-518.
Zheng J, Shen W, He DZ, Long KB, Madison LD, Dallos P (2000) Prestin is the motor protein of cochlear outer hair cells. Nature405:149-155.
Zhu Y, Zhao HB (2010) ATP-mediated potassium recycling in the cochlear supporting cells. Purinergic signalling6:221-229
Zhu Y, Liang C, Chen J, Zong L, Chen GD, Zhao HB.Active cochlear amplification is dependent on supporting cell gap junctions. Nat. Commun.4:1786doi:10.1038/ncomms2806(2013).
Ballinger SW, Shoffner JM, Hedaya EV, Trounce I, Polak MA, Koontz DA, Wallace DC (1992) Maternally transmitted diabetes and deafness associated with a10.4kb mitochondrial DNA deletion. Nature genetics1:11-15
Byers T, Bowman B (1993) Vitamin E supplements and coronary heart disease. Nutrition reviews51:333-336
Choi BH (1993) Oxygen, antioxidants and brain dysfunction. Yonsei medical journal 34:1-10
Davis RR, Newlander JK, Ling X, Cortopassi GA, Krieg EF, Erway LC (2001) Genetic basis for susceptibility to noise-induced hearing loss in mice. Hearing research155:82-90
DiMauro S, Bonilla E, Lombes A, Shanske S, Minetti C, Moraes CT (1990) Mitochondrial encephalomyopathies. Neurologic clinics8:483-506
Frolenkov GI (2006) Regulation of electromotility in the cochlear outer hair cell. The Journal of physiology576:43-48.
Gerbitz KD, Obermaier-Kusser B, Lestienne P, et al.(1990) Mutations of the mitochondrial DNA: the contribution of DNA techniques to the diagnosis of mitochondrial encephalomyopathies. Journal of clinical chemistry and clinical biochemistry. Zeitschrift for klinische Chemie und klinische Biochemie28:241-250
Gold M, Rapin I, Shanske S (1991) Mitochondrial inheritance of acquired deafness. Annals of the New York Academy of Sciences630:301-302
Grimes AM, Grady CL, Foster NL, Sunderland T, Patronas NJ (1985) Central auditory function in Alzheimer's disease. Neurology35:352-358
Grossman LI (1990) Mitochondrial DNA in sickness and in health. American journal of human genetics46:415-417
Halliwell B (1994) Free radicals and antioxidants:a personal view. Nutrition reviews52:253-265
Hiyama K, Hirai Y, Kyoizumi S, et al.(1995) Activation of telomerase in human lymphocytes and hematopoietic progenitor cells. Journal of immunology155:3711-3715
Hockenbery DM, Oltvai ZN, Yin XM, Milliman CL, Korsmeyer SJ (1993) Bcl-2functions in an antioxidant pathway to prevent apoptosis. Cell75:241-251
Huang T (2007) Age-related hearing loss. Minnesota medicine90:48-50
Ikeda K, Sunose H, Takase T. Effects of free radicals on in tracellular calcium concentration in the isolated outer hair cell of the guinea pig cochlea. Acta Ot olaryngol,1993;115:137
Johnson KR, Erway LC, Cook SA, Willott JF, Zheng QY (1997) A major gene affecting age-related hearing loss in C57BL/6J mice. Hearing research114:83-92
Kane DJ, Sarafian TA, Anton R, et al.(1993) Bcl-2inhibition of neural death:decreased generation of reactive oxygen species. Science262:1274-1277.
Lin MJ, Su MC, Tan CT, et al. The efect of larginine on slow motility of malnmalian outer hair cell. Hear Res,2003,178:52-58
Lyras L, Cairns NJ, Jenner A, Jenner P, Halliwell B (1997) An assessment of oxidative damage to proteins, lipids, and DNA in brain from patients with Alzheimer's disease. Journal of neurochemistry68:2061-2069
Miyabayashi S, Hanamizu H, Endo H, Tada K, Horai S (1991) A new type of mitochondrial DNA deletion in patients with encephalomyopathy. Journal of inherited metabolic disease14:805-812
Moon H, Baek D, Lee B, et al.(2002) Soybean ascorbate peroxidase suppresses Bax-induced apoptosis in yeast by inhibiting oxygen radical generation. Biochemical and biophysical research communications290:457-462.
Nagley P, Mackay IR, Baumer A, et al.(1992) Mitochondrial DNA mutation associated with aging and degenerative disease. Annals of the New York Academy of Sciences673:92-102
Nakashima T, Naganawa S. Disorders of cochlear blood flow. Brain Res Brain Res Rev.2003;43(1):17-28
Oliver D, He DZ, Klocker N, et al.(2001) Intracellular anions as the voltage sensor of prestin, the outer hair cell motor protein. Science292:2340-2343.
Olrvai ZN, Milliman CL, Korsmeyer SJ (1993) Bcl-2heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell74:609-619
Ospeck M, Dong XX, lwasa KH. Limiting frequency of the cochlear amplifier based on electromotility of outer hair cells. Biophys J,2003,84(2pt1):739-749
Pommier JP, Lebeau J, Ducray C, Sabatier L (1995) Chromosomal instability and alteration of telomere repeat sequences. Biochimie77:817-825
Prazma J, Carrasco VN, Butler B, Waters G, Anderson T, Pillsbury HC (1990) Cochlear microcirculation in young and old gerbils. Archives of otolaryngology-head&neck surgery116:932-936
Sawada S, Takeda T, Kakigi A, Saito H, Suehiro T, Nakauchi Y, Chikamori K (1997) Audiological findings of sensorineural deafness associated with a mutation in the mitochondrial DNA. The American journal of otology18:332-335
Seidman MD, Ahmad N, Bai U (2002) Molecular mechanisms of age-related hearing loss. Ageing research reviews1:331-343
Seidman MD, Khan MJ, Dolan DF, Quirk WS (1996) Age-related differences in cochlear microcirculation and auditory brain stem response. Archives of otolaryngology--head&neck surgery122:1221-1226
Seidman MD, Shivapuja BG, Quirk WS (1993) The protective effects of allopurinol and superoxide dismutase on noise-induced cochlear damage. Otolaryngology-head and neck surgery:official journal of American Academy of Otolaryngology-Head and Neck Surgery109:1052-1056
Serratrice G, Desnuelle C (1990)[Mitochondrial encephalomyopathies]. Presse medicale19:645-647
Sheehan JP, Swerdlow RH, Miller SW, Davis RE, Parks JK, Parker WD, Tuttle JB (1997) Calcium homeostasis and reactive oxygen species production in cells transformed by mitochondria from individuals with sporadic Alzheimer's disease. The Journal of neuroscience:the official journal of the Society for Neuroscience17:4612-4622
Simpson GV, Knight RT, Brailowsky S, Prospero-Garcia O, Scabini D (1985) Altered peripheral and brainstem auditory function in aged rats. Brain research348:28-35
Smith MA, Perry G (1995) Free radical damage, iron, and Alzheimer's disease. Journal of the neurological sciences134Suppl:92-94
Staecker H, Zheng QY, Van De Water TR (2001) Oxidative stress in aging in the C57B16/J mouse cochlea. Acta oto-laryngologica121:666-672
Strehler BL (1985) Aging:a challenge to science, society, and the individual. Clinics in geriatric medicine1:5-13
van den Ouweland JM, Lemkes HH, Ruitenbeek W, et al.(1992) Mutation in mitochondrial tRNA(Leu)(UUR) gene in a large pedigree with maternally transmitted type Ⅱ diabetes mellitus and deafness. Nature genetics1:368-371
Wallace DC (1997) Mitochondrial DNA in aging and disease. Scientific American277:40-47
Zenner K, Gold R, Meurers B, Reichmann H (1990)[Mitochondrial encephalomyopathies. A comparison of Kearns-Sayre syndrome, MELAS and MERRF]. Der Nervenarzt61:597-603
陈金(2010)Cav1.3钙离子通道蛋白在内耳的表达和年龄相关性听力损失的研究[D].华中科技大学(硕士论文)