Anchored PKA synchronizes adrenergic phosphoregulation of cardiac Ca_v1.2 channels.

ABSTRACT: Adrenergic modulation of voltage gated Ca²⁺ currents is a context specific process. In the heart Ca_v1.2 channels initiate excitation-contraction coupling. This requires PKA phosphorylation of the small GTPase Rad (Ras associated with diabetes) and involves direct phosphorylation of the Ca_v1.2 α₁ subunit at Ser1700. A contributing factor is the proximity of PKA to the channel through association with A-kinase anchoring proteins (AKAPs). Disruption of PKA anchoring by the disruptor peptide AKAP-IS prevents upregulation of Ca_v1.2 currents in tsA-201 cells. Biochemical analyses demonstrate that Rad does not function as an AKAP. Electrophysiological recording shows that channel mutants lacking phosphorylation sites (Ca_v1.2 STAA)

SUBMITTER: Wang L 

PROVIDER: S-EPMC11408856 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature