Repertoire of high voltage-activated Ca2+ channels in the lateral superior olive: functional analysis in wild-type, Cav1.3-/-, and Cav1.2DHP-/- mice
Repertoire of high voltage-activated Ca2+ channels in the lateral superior olive: functional analysis in wild-type, Cav1.3-/-, and Cav1.2DHP-/- mice
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DOI：
10.1152/jn.00948.2011
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发表时间：
2012-07-01
影响因子：
2.5
通讯作者：
Friauf, Eckhard
中科院分区：
文献类型：
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作者：
Jurkovicova-Tarabova, Bohumila;Griesemer, Desiree;Friauf, Eckhard
[11]杨文，李文.外侧上级橄榄体中高压激活的钙通道库：野生型、Ca（v）1.3（-/-）和Ca（v）1.2DHP（-/-）小鼠的功能分析J Neurophysiol 108：365-379，2012.首次发表于2012年4月25日; doi：10.1152/jn.00948.2011.-高电压激活钙通道（HVACCs）的电压门控钙通道（Ca-v）1.3 α亚基是耳蜗内毛细胞钙内流和递质释放的重要通道，也是听觉信号传入中枢的重要通道。它们的缺失导致耳聋和听觉脑干的显著结构变化，特别是外侧上级橄榄（LSO）。在这里，我们分析了各种类型的HVACCs的总钙电流（I-Ca）在发展中的小鼠LSO神经元的贡献，以解决几个问题：LSO神经元表达功能性Ca（v）1.3通道？还有哪些其他类型的HVACCs被表达？是否有发展变化？Ca（v）1.3（-/-）小鼠的LSO神经元是否表现出任何代偿反应，即其他HVACCs的上调？我们的电生理学和药理学结果表明，在出生后第4天和第12天，存在功能性Ca（v）1.3和Ca（v）1.2通道。除了这些L型通道，LSO神经元还表达功能性P/Q型、N型和最可能的R型通道。出生后12天，四种不同亚型对I-Ca的相对贡献分别为45%、29%、22%和4%。生理结果侧翼和定量RT-PCR数据扩展。总之，LSO神经元显示了广泛的剧目HVACC亚型。Ca（v）1.3基因的消除导致了其他一些HVACCs的功能重组，但没有恢复正常的I-Ca特性。总之，我们的研究结果表明，几种类型的HVACCs的功能相关的发展LSO。Ca（v）1.3的现场损失，即，在LSO神经元中，导致最近描述的LSO畸形需要通过使用组织特异性Ca（v）1.3（-/-）动物来确定。
Jurkovicova-Tarabova B, Griesemer D, Pirone A, Sinnegger-Brauns MJ, Striessnig J, Friauf E. Repertoire of high voltage-activated Ca2+ channels in the lateral superior olive: functional analysis in wild-type, Ca(v)1.3(-/-), and Ca(v)1.2DHP(-/-) mice. J Neurophysiol 108: 365-379, 2012. First published April 25, 2012; doi:10.1152/jn.00948.2011.-Voltage-gated Ca2+ (Ca-v)1.3 alpha-subunits of high voltage-activated Ca2+ channels (HVACCs) are essential for Ca2+ influx and transmitter release in cochlear inner hair cells and therefore for signal transmission into the central auditory pathway. Their absence leads to deafness and to striking structural changes in the auditory brain stem, particularly in the lateral superior olive (LSO). Here, we analyzed the contribution of various types of HVACCs to the total Ca2+ current (I-Ca) in developing mouse LSO neurons to address several questions: do LSO neurons express functional Ca(v)1.3 channels? What other types of HVACCs are expressed? Are there developmental changes? Do LSO neurons of Ca(v)1.3(-/-) mice show any compensatory responses, namely, upregulation of other HVACCs? Our electrophysiological and pharmacological results showed the presence of functional Ca(v)1.3 and Ca(v)1.2 channels at both postnatal days 4 and 12. Aside from these L-type channels, LSO neurons also expressed functional P/Q-type, N-type, and, most likely, R-type channels. The relative contribution of the four different subtypes to I-Ca appeared to be 45%, 29%, 22%, and 4% at postnatal day 12, respectively. The physiological results were flanked and extended by quantitative RT-PCR data. Altogether, LSO neurons displayed a broad repertoire of HVACC subtypes. Genetic ablation of Ca(v)1.3 resulted in functional reorganization of some other HVACCs but did not restore normal I-Ca properties. Together, our results suggest that several types of HVACCs are of functional relevance for the developing LSO. Whether on-site loss of Ca(v)1.3, i.e., in LSO neurons, contributes to the recently described malformation of the LSO needs to be determined by using tissue-specific Ca(v)1.3(-/-) animals.