Targeted mutation of Ser(1928) to alanine in Cav1.2 abolished phosphorylation by PKA but did not affect basal L-type current characteristics or its regulation by PKA and beta-adrenergic receptors.
PKA phosphorylation of Ser(1928) of Ca(v)1.2 is not functionally required for beta-adrenergic stimulation of L-type calcium channels in cardiomyocytes.
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.
Lemke et al. (2008) studied this question. Targeted mutation of Ser(1928) to alanine in Cav1.2 vs. Wild-type was evaluated on L-type current characteristics and regulation by PKA and beta-adrenergic receptor. Targeted mutation of Ser(1928) to alanine in Cav1.2 abolished phosphorylation by PKA but did not affect basal L-type current characteristics or its regulation by PKA and beta-adrenergic receptors.