Alpha-Actinin Promotes Surface Localization and Ion Conducting Activity of the L-Type Ca2+ Channel by Binding to the IQ Region of CaV1.2

Abstract

Integrator 1 (BIN1), in the clustering of Ca v 1.2 channels in ventricular myocytes. Both of these proteins are known to directly interact with Ca v 1.2 channels. AKAP150 is important for local membrane targeting of PKA, PKCa and calcineurin, while Bin1 has established roles in cardiac t-tubule folding and in the trafficking and localization of Ca v 1.2 channels to t-tubules. Using GSD superresolution imaging, we found that clustering of Ca v 1.2 channels in these cells is unaltered by genetic ablation of AKAP79/150 such that the area of Ca V 1.2 clusters was similar in WT (2379 5 43 nm) and AKAP150 -/myocytes (2379 5 43 nm). However, heterozygous deletion of Bin1 significantly reduced Ca v 1.2 channel cluster size. The area of Ca V 1.2 channel clusters was approximately 42% smaller in BIN1 þ/-(1379 5 43 nm) than in WT (2349 5 76 nm 2 ) ventricular myocytes (p< 0.0001). This data suggests that Bin1 is a key regulator of Ca v 1.2 channel clustering in heart.