Proteins of the Triadic Excitation–Contraction Coupling Complex in Skeletal Muscle

Excitation-contraction coupling (ECC) in skeletal muscle is mediated by mechanical coupling between the L-type voltage-dependent Ca²⁺ channel (Ca_V1.1) in the transverse tubules and the Ca²⁺ release channel (RYR1) in the sarcoplasmic reticulum (SR). However, ECC complexes are much more complicated than just these two ion channels. Triadic Ca²⁺ release units (CRUs) that mediate ECC in skeletal muscle are allosterically regulated complexes of ion channels, cytoplasmic modulators, SR transmembrane proteins, and lumenal Ca²⁺ buffers. While RYR1, Ca_V1.1α_1s, and Ca_V1.1β_1a, the SH3 and cysteine-rich domain protein (STAC3) and junctophilin (JPH1 and/or JPH2) are required for voltage-gated Ca²⁺ 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.