Congenital deafness and sinoatrial node dysfunction in mice lacking class D L-type Ca2+ channels
Congenital deafness and sinoatrial node dysfunction in mice lacking class D L-type Ca2+ channels
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DOI：
10.1016/s0092-8674(00)00013-1
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发表时间：
2000-07-07
期刊：
影响因子：
64.5
通讯作者：
Striessnig, J
中科院分区：
文献类型：
--
作者：
Platzer, J;Engel, J;Striessnig, J
电压依赖性L型钙离子通道（LTCCs）含有一个成孔α 1D亚基（D-LTCCs），在神经元和神经内分泌细胞中表达。它们对总L-型Ca 2+电流的相对贡献及其作为药物靶点的生理作用和意义仍然未知。因此，我们产生了D-LTCC缺陷型小鼠（α 1D（-/-）），这些小鼠是存活的，没有葡萄糖代谢的重大障碍。α 1D（-/-）小鼠由于耳蜗内毛细胞中完全缺乏L型电流以及外毛细胞和内毛细胞的变性而耳聋。在野生型对照中，D-LTCC介导的电流显示低激活阈值和缓慢失活动力学。心电图记录显示α 1D（-/-）小鼠的窦房结功能障碍（心动过缓和心律失常）。我们的结论是，α 1D可以形成LTCC与负激活阈值的正常听觉功能和心脏起搏器活动的控制是必不可少的。
Voltage-Elated L-type Ca2+ channels (LTCCs) containing a pore-forming alpha 1D subunit (D-LTCCs) are expressed in neurons and neuroendocrine cells. Their relative contribution to total L-type Ca2+ currents and their physiological role and significance as a drug target remain unknown. Therefore, we generated D-LTCC deficient mice (alpha 1D(-/-)) that were viable with no major disturbances of glucose metabolism. alpha 1D(-/-) mice were deaf due to the complete absence of L-type currents in cochlear inner hair cells and degeneration of outer and inner hair cells. In wild-type controls, D-LTCC-mediated currents showed low activation thresholds and slow inactivation kinetics. Electrocardiogram recordings revealed sinoatrial node dysfunction (bradycardia and arrhythmia) in alpha 1D(-/-) mice. We conclude that alpha 1D can form LTCCs with negative activation thresholds essential for normal auditory function and control of cardiac pacemaker activity.