Rem uncouples excitation–contraction coupling in adult skeletal muscle fibers

摘要: In skeletal muscle, excitation–contraction (EC) coupling requires depolarization-induced conformational rearrangements in L-type Ca2+ channel (CaV1.1) to be communicated the type 1 ryanodine-sensitive release (RYR1) of sarcoplasmic reticulum (SR) via transient protein–protein interactions. Although molecular mechanism that underlies between CaV1.1 and RYR1 has been investigated intensely for more than 25 years, question whether such signaling occurs a direct interaction principal, voltage-sensing α1S subunit or through an intermediary protein persists. A substantial body evidence supports idea auxiliary β1a is conduit this intermolecular communication. However, role difficult test because serves two other functions are prerequisite RYR1. Specifically, promotes efficient membrane expression facilitates tetradic ultrastructural arrangement channels within plasma membrane–SR junctions. paper, we demonstrate overexpression RGK Rem, established β subunit–interacting protein, adult mouse flexor digitorum brevis fibers markedly reduces voltage-induced myoplasmic transients without greatly affecting targeting, intramembrane gating charge movement, releasable SR store content. contrast, β1a-binding–deficient Rem triple mutant (R200A/L227A/H229A) little effect on response depolarization. Thus, effectively uncouples voltage sensors from RYR1-mediated its ability interact with β1a. Our findings reveal Rem-expressing muscle as experimental system may prove useful definition precise skeletal-type EC coupling.