Figure 2. Stress responses in skeletal muscle during E-C coupling.

Depolarization of the T-tubule membrane activates Cav1.1, triggering SR Ca²⁺ release through RyR1 and leading to sarcomere contraction, a process known as E-C coupling. Intracellular signaling pathways activated in skeletal muscle by pathological stress affect RyR1 function and alter E-C coupling. Stress-induced RyR1 dysfunction can result in SR Ca²⁺ leak, which potentially activates numerous Ca²⁺-dependent cellular damage mechanisms. AC, adenylate cyclase.