Isoproterenol Promotes Rapid Ryanodine Receptor Movement to Bridging Integrator 1 (BIN1)-Organized Dyads.

ABSTRACT:

Background

The key pathophysiology of human acquired heart failure is impaired calcium transient, which is initiated at dyads consisting of ryanodine receptors (RyRs) at sarcoplasmic reticulum apposing CaV1.2 channels at t-tubules. Sympathetic tone regulates myocardial calcium transients through β-adrenergic receptor (β-AR)-mediated phosphorylation of dyadic proteins. Phosphorylated RyRs (P-RyR) have increased calcium sensitivity and open probability, amplifying calcium transient at a cost of receptor instability. Given that bridging integrator 1 (BIN1) organizes t-tubule microfolds and facilitates CaV1.2 delivery, we explored whether β-AR-regulated RyRs are also affected by BIN1.

Methods and results

Isolated adult mouse hearts or cardiomyocytes were perfused for 5 minutes w

SUBMITTER: Fu Y 

PROVIDER: S-EPMC4729615 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature