β-adrenergic-mediated dynamic augmentation of sarcolemmal Ca_V 1.2 clustering and co-operativity in ventricular myocytes.

ABSTRACT:

Key points

Prevailing dogma holds that activation of the β-adrenergic receptor/cAMP/protein kinase A signalling pathway leads to enhanced L-type Ca_V 1.2 channel activity, resulting in increased Ca²⁺ influx into ventricular myocytes and a positive inotropic response. However, the full mechanistic and molecular details underlying this phenomenon are incompletely understood. Ca_V 1.2 channel clusters decorate T-tubule sarcolemmas of ventricular myocytes. Within clusters, nanometer proximity between channels permits Ca²⁺ -dependent co-operative gating behaviour mediated by physical interactions between adjacent channel C-terminal tails. We report that stimulation of cardiomyocytes with isoproterenol, evokes dynamic, protein kinase A-dependent

SUBMITTER: Ito DW 

PROVIDER: S-EPMC6462464 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature