Bin1 Regulates CaV1.2 Channel Clustering in Ventricular Myocytes

摘要: L-type Cav1.2 channels are expressed in the plasma membranes of excitable cells including cardiac myocytes where they play a key role excitation-contraction coupling. Recently, we reported that form clusters undergo dynamic, reciprocal, allosteric interactions. This ‘functional coupling’ facilitates Ca2+ influx by increasing activity (NPo) adjoined and occurs through C-terminal-to-C-terminal Physical proximity on membrane is an essential requirement for functional interactions channels. In present study, investigated two scaffolding proteins, A-Kinase Anchoring Protein 150 (AKAP150) Bridging Integrator 1 (BIN1), clustering ventricular myocytes. Both these proteins known to directly interact with AKAP150 important local targeting PKA, PKCα calcineurin, while Bin1 has established roles t-tubule folding trafficking localization t-tubules. Using GSD super-resolution imaging, found unaltered genetic ablation AKAP79/150 such area CaV1.2 was similar WT (2379 ± 43 nm) AKAP150-/- nm). However, heterozygous deletion significantly reduced channel cluster size. The approximately 42% smaller BIN1+/- (1379 than (2349 76 nm2) (p< 0.0001). data suggests regulator heart.