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Review
. 2025 Oct 1;17(10):a041482.
doi: 10.1101/cshperspect.a041482.

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

Ting Chang #  1 , Rachel Sue Zhen Yee #  1 , George G Rodney  1 , Susan L Hamilton  2
Affiliations
Review

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

Ting Chang et al. Cold Spring Harb Perspect Biol. .

Abstract

Excitation-contraction coupling (ECC) in skeletal muscle is mediated by mechanical coupling between the L-type voltage-dependent Ca2+ channel (CaV1.1) 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, CaV1.1α1s, and CaV1.1β1a, 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.

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