Stockner Thomas, Koschak Alexandra
Medical University Vienna, Center for Physiology and Pharmacology, Department of Pharmacology, Währingerstrasse 13A, 1090 Vienna, Austria.
Biochim Biophys Acta. 2013 Jul;1828(7):1598-607. doi: 10.1016/j.bbamem.2012.11.026. Epub 2012 Dec 4.
Voltage-gated Ca²⁺ channels allow for Ca²⁺-dependent intracellular signaling by directly mediating Ca²⁺ ion influx, by physical coupling to intracellular Ca²⁺ release channels or functional coupling to other ion channels such as Ca²⁺ activated potassium channels. L-type Ca²⁺ channels that comprise the family of Ca(v)1 channels are expressed in many electrically excitable tissues and are characterized by their unique sensitivity to dihydropyridines. In this issue, we summarize genetic defects in L-type Ca²⁺ channels and analyze their role in human diseases (Ca²⁺ channelopathies); e.g. mutations in Ca(v)1.2 α1 cause Timothy and Brugada syndrome, mutations in Ca(v)1.3 α1 are linked to sinoatrial node dysfunction and deafness while mutations in Ca(v)1.4 α1 are associated with X-linked retinal disorders such as an incomplete form of congenital stationary night blindness. Herein, we also put the mutations underlying the channel's dysfunction into the structural context of the pore-forming α1 subunit. This analysis highlights the importance of combining functional data with structural analysis to gain a deeper understanding for the disease pathophysiology as well as for physiological channel function. This article is part of a Special Issue entitled: Calcium channels.
电压门控性Ca²⁺通道通过直接介导Ca²⁺离子内流、与细胞内Ca²⁺释放通道进行物理偶联或与其他离子通道（如Ca²⁺激活的钾通道）进行功能偶联，实现依赖Ca²⁺的细胞内信号传导。构成Ca(v)1通道家族的L型Ca²⁺通道在许多电兴奋性组织中表达，其特点是对二氢吡啶具有独特的敏感性。在本期中，我们总结了L型Ca²⁺通道的遗传缺陷，并分析了它们在人类疾病（Ca²⁺通道病）中的作用；例如，Ca(v)1.2 α1亚基的突变会导致蒂莫西综合征和布加综合征，Ca(v)1.3 α1亚基的突变与窦房结功能障碍和耳聋有关，而Ca(v)1.4 α1亚基的突变与X连锁视网膜疾病相关，如不完全型先天性静止性夜盲。在此，我们还将导致通道功能障碍的突变置于形成孔道的α1亚基的结构背景中。该分析强调了将功能数据与结构分析相结合对于深入理解疾病病理生理学以及生理通道功能的重要性。本文是名为“钙通道”的特刊的一部分。
