4.8 Article

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


DOI: 10.1073/pnas.2207887120


heart; ion transport; acylation; excitation-contraction; excitation-contraction coupling

Ask authors/readers for more resources

The α1C subunit of L-type Ca2+ channels, responsible for transmembrane Ca2+ fluxes, undergoes reversible palmitoylation in rat, rabbit, and human ventricular myocytes. The sites of palmitoylation are found in the N terminus and the linker between domains I and II of the channel. Unpalmitoylated α1C subunit leads to reduced voltage sensitivity of Ca2+ channels.
Mammalian voltage-activated L-type Ca2+ channels, such as Ca(v)1.2, control transmem-brane Ca2+ fluxes in numerous excitable tissues. Here, we report that the pore-forming & alpha;1C 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 termi-nus 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 & alpha;1C was not palmi-toylated. To examine function, we expressed dihydropyridine-resistant & alpha;1C 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 by unpalmitoylatable channels displayed a similar activation time course but signifi-cantly reduced amplitude compared to those generated by wild-type channels. We thus conclude that palmitoylation controls the voltage sensitivity of Ca(v)1.2. Given that the identified Ca(v)1.2 palmitoylation sites are also conserved in most Ca(v)1 isoforms, we propose that palmitoylation of the pore-forming & alpha;1C subunit provides a means to regulate the voltage sensitivity of voltage-activated Ca2+ channels in excitable cells.


I am an author on this paper
Click your name to claim this paper and add it to your profile.


Primary Rating

Not enough ratings

Secondary Ratings

Scientific rigor
Rate this paper


No Data Available
No Data Available