Unchanged β-Adrenergic Stimulation of Cardiac L-type Calcium Channels in Cav1.2 Phosphorylation Site S1928A Mutant Mice

作者：Toni Lemke, Andrea Welling, Carl J. Christel, Anne Blaich, Dominik Bernhard, Peter Lenhardt, Franz Bruno Hofmann, Sven Moosmang · 发表于：Journal of Biological Chemistry · 年份：2008 · DOI：10.1074/jbc.m804981200 · 被引用次数：136 · 研究领域：Cardiac electrophysiology and arrhythmias、Ion channel regulation and function、Receptor Mechanisms and Signaling

Phosphorylation of serine 1928 (Ser(1928)) of the cardiac Ca(v)1.2 subunit of L-type Ca(2+) channels has been proposed as the mechanism for regulation of L-type Ca(2+) channels by protein kinase A (PKA). To test this directly in vivo, we generated a knock-in mouse with targeted mutation of Ser(1928) to alanine. This mutation did not affect basal L-type current characteristics or regulation of the L-type current by PKA and the beta-adrenergic receptor, whereas the mutation abolished phosphorylation of Ca(v)1.2 by PKA. Therefore, our data show that PKA phosphorylation of Ser(1928) of Ca(v)1.2 is not functionally involved in beta-adrenergic stimulation of Ca(v)1.2-mediated Ca(2+) influx into the cardiomyocyte.