PKA phosphorylation underlies functional recruitment of sarcolemmal SK2 channels in ventricular myocytes from hypertrophic hearts.

ABSTRACT:

Key points

Small-conductance Ca²⁺ -activated K⁺ (SK) channels expressed in ventricular myocytes are dormant in health, yet become functional in cardiac disease. SK channels are voltage independent and their gating is controlled by intracellular [Ca²⁺ ] in a biphasic manner. Submicromolar [Ca²⁺ ] activates the channel via constitutively-bound calmodulin, whereas higher [Ca²⁺ ] exerts inhibitory effect during depolarization. Using a rat model of cardiac hypertrophy induced by thoracic aortic banding, we found that functional upregulation of SK2 channels in hypertrophic rat ventricular cardiomyocytes is driven by protein kinase A (PKA) phosphorylation. Using site-directed mutagenesis, we identified serine-465 as the site conferrin

SUBMITTER: Hamilton S 

PROVIDER: S-EPMC7496687 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature