Pitt Geoffrey S, Matsui Maiko, Cao Chike
Cardiovascular Research Institute, Weill Cornell Medicine, New York, NY 10021, USA; email:
Annu Rev Physiol. 2021 Feb 10;83:183-203. doi: 10.1146/annurev-physiol-031620-091043. Epub 2020 Oct 26.
The identification of a gain-of-function mutation in as the cause of Timothy syndrome, a rare disorder characterized by cardiac arrhythmias and syndactyly, highlighted roles for the L-type voltage-gated Ca channel Ca1.2 in nonexcitable cells. Previous studies in cells and animal models had suggested that several voltage-gated Ca channels (VGCCs) regulated critical signaling events in various cell types that are not expected to support action potentials, but definitive data were lacking. VGCCs occupy a special position among ion channels, uniquely able to translate membrane excitability into the cytoplasmic Ca changes that underlie the cellular responses to electrical activity. Yet how these channels function in cells not firing action potentials and what the consequences of their actions are in nonexcitable cells remain critical questions. The development of new animal and cellular models and the emergence of large data sets and unbiased genome screens have added to our understanding of the unanticipated roles for VGCCs in nonexcitable cells. Here, we review current knowledge of VGCC regulation and function in nonexcitable tissues and cells, with the goal of providing a platform for continued investigation.
在 Timothy 综合征（一种以心律失常和并指为特征的罕见疾病）中发现功能获得性突变，这凸显了 L 型电压门控钙通道 Ca1.2 在非兴奋性细胞中的作用。先前在细胞和动物模型中的研究表明，几种电压门控钙通道（VGCCs）在各种预计不支持动作电位的细胞类型中调节关键信号事件，但缺乏确凿的数据。VGCCs 在离子通道中占据特殊位置，能够独特地将膜兴奋性转化为细胞质钙变化，而这种变化是细胞对电活动反应的基础。然而，这些通道在不产生动作电位的细胞中如何发挥作用以及它们在非兴奋性细胞中的作用后果仍然是关键问题。新的动物和细胞模型的开发以及大数据集和无偏基因组筛选的出现，加深了我们对 VGCCs 在非兴奋性细胞中意外作用的理解。在这里，我们回顾了当前关于 VGCCs 在非兴奋性组织和细胞中的调节和功能的知识，目的是提供一个持续研究的平台。
