Abstract
Excitation-contraction coupling (ECC) in skeletal muscle is mediated by mechanical coupling between the L-type voltage-dependent Ca(2+) channel (Ca(V)1.1) in the transverse tubules and the Ca(2+) release channel (RYR1) in the sarcoplasmic reticulum (SR). However, ECC complexes are much more complicated than just these two ion channels. Triadic Ca(2+) release units (CRUs) that mediate ECC in skeletal muscle are allosterically regulated complexes of ion channels, cytoplasmic modulators, SR transmembrane proteins, and lumenal Ca(2+) buffers. While RYR1, Ca(V)1.1α(1s), and Ca(V)1.1β(1a), the SH3 and cysteine-rich domain protein (STAC3) and junctophilin (JPH1 and/or JPH2) are required for voltage-gated Ca(2+) release, other auxiliary proteins modulate this process. In this review, we discuss what is known about the proteins in the triadic protein complex, their roles in ECC, and the mutations in the ECC proteins that give rise to skeletal muscle myopathies.