Tuning EC-Coupling: β-Adrenergic Receptor Activation Stimulates Dynamic Augmentation of CaV1. 2 Channel Sarcolemmal Abundance and Cooperativity

摘要: Voltage-gated L-type CaV1.2 channels play an essential role in cardiac excitation-contraction coupling. These channels decorate the z-lines of ventricular myocytes where they form discrete clusters on the t-tubule membrane. We have previously reported that groups of channels within these clusters are capable of influencing each other’s gating behavior and undergo dynamic, cooperative interactions. This occurs via Ca2+-calmodulin-dependent, physical interactions between the C-terminal tails of adjacent channels. The interactions increase the open probability (Po) of adjoined channels, and thus amplify Ca2+ influx into the myocytes. It has long been known that activation of β-adrenergic receptors during the ‘fight or flight’ response, leads to increased mean open time and Po of CaV1.2 channels, and thus enhanced Ca2+ influx. Given our previous finding that CaV1.2 channel cooperativity is triggered by Ca2 …