Palmitoylation of the pore-forming subunit of Ca(v)1.2 controls channel voltage sensitivity and calcium transients in cardiac myocytes.

ABSTRACT: Mammalian voltage-activated L-type Ca²⁺ channels, such as Ca(v)1.2, control transmembrane Ca²⁺ fluxes in numerous excitable tissues. Here, we report that the pore-forming α1C subunit of Ca(v)1.2 is reversibly palmitoylated in rat, rabbit, and human ventricular myocytes. We map the palmitoylation sites to two regions of the channel: The N terminus and the linker between domains I and II. Whole-cell voltage clamping revealed a rightward shift of the Ca(v)1.2 current-voltage relationship when α1C was not palmitoylated. To examine function, we expressed dihydropyridine-resistant α1C in human induced pluripotent stem cell-derived cardiomyocytes and measured Ca²⁺ transients in the presence of nifedipine to block the endogenous channels. The transients generated b

SUBMITTER: Kuo CS 

PROVIDER: S-EPMC9963536 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature