Coupling of Smoothened to inhibitory G proteins reduces voltage-gated K⁺ currents in cardiomyocytes and prolongs cardiac action potential duration.

ABSTRACT: SMO (Smoothened), the central transducer of Hedgehog signaling, is coupled to heterotrimeric G_i proteins in many cell types, including cardiomyocytes. In this study, we report that activation of SMO with SHH (Sonic Hedgehog) or a small agonist, purmorphamine, rapidly causes a prolongation of the action potential duration that is sensitive to a SMO inhibitor. In contrast, neither of the SMO agonists prolonged the action potential in cardiomyocytes from transgenic G_iCT/TTA mice, in which G_i signaling is impaired, suggesting that the effect of SMO is mediated by G_i proteins. Investigation of the mechanism underlying the change in action potential kinetics revealed that activation of SMO selectively reduces outward voltage-gated K⁺ repolar

SUBMITTER: Cheng L 

PROVIDER: S-EPMC6052211 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature