Phosphorylation of Ser 1928 mediates the enhanced activity of the L-type Ca 2+ channel Ca v 1.2 by the β 2 -adrenergic receptor in neurons

The L-type Ca2+ channel Cav1.2 controls heart rate and neuronal excitability. Qian et al . found that enhancement of Cav1.2 channel activity in the brain by β-adrenergic receptor (βAR) signaling required phosphorylation of Ser1928, whereas in the heart, this site was dispensable for βAR-mediated regulation. In contrast to those from wild-type mice, hippocampal neurons from mice, in which Ser1928 of Cav1.2 was mutated to alanine, did not exhibit increased L-type calcium channel activity in response to β-adrenergic stimulation. Phosphorylation of Ser1928 involved signaling through the β2AR, but not through the β1AR, and this phosphorylation event enabled a particular form of long-term potentiation, a process linked to learning and memory. These results were in marked contrast to βAR-mediated regulation of Cav1.2 activity in cardiomyocytes, which involved β1AR and was independent of Ser1928. This differential regulation in the heart and brain implies that tissue-specific therapeutics could be identified.