Title | Voltage-Gated Calcium Channels in Nonexcitable Tissues. |
Publication Type | Journal Article |
Year of Publication | 2021 |
Authors | Pitt GS, Matsui M, Cao C |
Journal | Annu Rev Physiol |
Volume | 83 |
Pagination | 183-203 |
Date Published | 2021 02 10 |
ISSN | 1545-1585 |
Abstract | The identification of a gain-of-function mutation in CACNA1C as the cause of Timothy syndrome, a rare disorder characterized by cardiac arrhythmias and syndactyly, highlighted roles for the L-type voltage-gated Ca2+ channel CaV1.2 in nonexcitable cells. Previous studies in cells and animal models had suggested that several voltage-gated Ca2+ 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 Ca2+ 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. |
DOI | 10.1146/annurev-physiol-031620-091043 |
Alternate Journal | Annu Rev Physiol |
PubMed ID | 33106102 |
Grant List | R01 HD090132 / HD / NICHD NIH HHS / United States R01 HL113136 / HL / NHLBI NIH HHS / United States |