Unchanged β-adrenergic stimulation of cardiac L-type calcium channels in Cav1.2 phosphorylation site S1928A mutant mice

Abstract

Phosphorylation of serine 1928 (Ser1928) of the cardiac Ca v1.2 subunit of L-type Ca2+ channels has been proposed as the mechanism for regulation of L-type Ca2+ channels by protein kinase A (PKA). To test this directly in vivo, we generated a knock-in mouse with targeted mutation of Ser1928 to alanine. This mutation did not affect basal L-type current characteristics or regulation of the L-type current by PKA and the β-adrenergic receptor, whereas the mutation abolished phosphorylation of Cav1.2 by PKA. Therefore, our data show that PKA phosphorylation of Ser1928 of Cav1.2 is not functionally involved in β-adrenergic stimulation of Cav1.2-mediated Ca2+ influx into the cardiomyocyte. © 2008 by The American Society for Biochemistry and Molecular Biology, Inc.