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首页> 外文期刊>Channels >Ba2+ currents in inner and outer hair cells of mice lacking the voltage-dependent Ca2+ channel subunits beta 3 or beta 4
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Ba2+ currents in inner and outer hair cells of mice lacking the voltage-dependent Ca2+ channel subunits beta 3 or beta 4

机译：缺少电压依赖性Ca2 +通道亚基beta 3或beta 4的小鼠的内，外毛细胞中的Ba2 +电流

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摘要

Voltage-activated Ca2+ channels comprise complexes of a pore-forming Ca-V alpha(1) and auxiliary subunits Ca-V beta, Ca-V alpha(2)delta and sometimes Ca-V gamma. The intracellular Ca-V beta subunit assists in trafficking and surface expression of the Ca-V alpha(1) subunit and can modulate biophysical properties of the Ca2+ channel. Four genes, Ca-V beta 1-4, exist which confer different properties to Ca2+ currents through the various Ca-V alpha(1) subunits. Ca2+ currents in cochlear inner (IHC) and outer hair cells (OHC) serving synaptic transmission flow predominantly through the L-type CaVa1 subunit Ca(V)1.3, but associated Ca-V beta subunits are unknown. In the organ of Corti, we found mRNA and protein for all four Ca-V beta subunits including Ca-V beta 2, but clear assignment of the Ca-V beta 1-4 immunolabelling with hair cells or nerve fibers was difficult. We analyzed Ca-V beta 3 knockout (Ca-V beta 3(-/-))and Ca-V beta 4 mutant mice (Ca-V beta 4(lh/lh)), which had normal hearing. Recording voltage-activated Ba2+ currents from hair cells of the two mouse models revealed distinct significant changes of cell size and Ba2+ current properties compared with their wild-type controls. Neonatal Ca-V beta 4(lh/lh) IHCs showed reduced membrane capacitances and changes in the voltage dependence and kinetics of current activation, whereas mature IHCs had reduced peak currents compared with Ca-V beta 4(wt), altogether indicating the presence of Ca-V beta 4 in IHCs. Ba2+ currents of Ca-V beta 3(-/-) OHCs showed largely reduced amplitudes, changes in the voltage dependence and kinetics of Ba2+ current activation, and increased inactivation compared with Ca-V beta 3(wt), pointing to a role of Ca-V beta 3 for OHCs. These results indicate that neither Ca-V beta 3 nor Ca-V beta 4 are indispensable for hair cell Ca2+ currents but contribute to the overall current properties.
机译：电压激活的Ca2 +通道包含形成孔的Ca-V alpha（1）和辅助亚基Ca-V beta，Ca-V alpha（2）δ以及有时是Ca-V gamma的复合物。细胞内的Ca-Vβ亚基可协助Ca-V alpha（1）亚基的运输和表面表达，并可调节Ca2 +通道的生物物理特性。存在四个基因Ca-V beta 1-4，它们通过各种Ca-V alpha（1）亚基赋予Ca2 +电流不同的特性。耳蜗内（IHC）和外毛细胞（OHC）的突触传递中的Ca2 +电流主要流经L型CaVa1亚基Ca（V）1.3，但相关的Ca-Vβ亚基尚不清楚。在Corti器官中，我们发现了包括Ca-V beta 2在内的所有四个Ca-V beta亚基的mRNA和蛋白质，但是很难明确分配Ca-V beta 1-4免疫标记与毛细胞或神经纤维。我们分析了听力正常的Ca-V beta 3基因敲除（Ca-V beta 3（-/-））和Ca-V beta 4突变小鼠（Ca-V beta 4（lh / lh））。记录来自两个小鼠模型的毛细胞的电压激活的Ba2 +电流，与野生型对照相比，揭示了细胞大小和Ba2 +电流特性的明显不同。新生的Ca-V beta 4（lh / lh）IHCs减少了膜电容，并改变了电压依赖性和电流激活动力学，而成熟的IHCs与Ca-V beta 4（wt）相比，峰值电流降低，表明存在IHC中Ca-V beta 4的含量。与Ca-V beta 3（wt）相比，Ca-V beta 3（-/-）OHC的Ba2 +电流显示出大幅降低的幅度，Ba2 +电流激活的电压依赖性和动力学变化以及失活增加，这表明用于OHC的Ca-V beta 3。这些结果表明，Ca-V beta 3和Ca-V beta 4都不是毛细胞Ca2 +电流必不可少的，但有助于总体电流特性。

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