Figure 1.

The EC coupling multi-protein complex of skeletal muscle. (A) Proteins involved in TT-SR junction formation and TT membrane voltage control of SR Ca²⁺ release. The TT of mammalian skeletal muscle fibers express the Ca_V1.1 complex responsible for the L-type Ca²⁺ inward current, which consists of the channel forming α_1s protein and auxiliary subunits α₂δ-1, β_1a, and γ₁. Up to four Ca_V1.1 channels can be associated with one homo-tetrameric Ca²⁺ release channel RYR1. Conformational communication with RYR1 requires further proteins, STAC3, and junctophilins (JP1 and JP2). Highlighted in red is the minimal set of molecular components that allowed functional reconstitution of voltage-dependent Ca²⁺ release after heterologous expression in non-muscle cells (Perni et al., 2017). (B) Proteins expressed in the study by El Ghaleb et al. (2022) in HEK293 cells to investigate the impact of the γ₁ subunit and a 19 amino acid stretch in the domain IV S3–S4 linker of α_1s that is absent in the embryonic splice variant Ca_V1.1e and present in adult Ca_V1.1a (both structures indicated in yellow). (C) Alterations of functional characteristics of Ca_V1.1a and Ca_V1.1e caused by co-expressing γ₁. Inactivation (VDI) and surface expression are comparably enhanced, but L-type Ca²⁺ current density is only reduced from a relatively high level in combination with the adult splice variant Ca_V1.1a (El Ghaleb et al., 2022).