On the footsteps of Triadin and its role in skeletal muscle

Figure 2 Proposed model of Ca²⁺ regulation by Triadin in wild-type and Triadin-null skeletal muscle. Lack of Triadin binding to type-1 ryanodine receptor (RyR1) indirectly affects FKBP12/RyR1 interaction causing, on the one hand, an increase in RyR1 channel gating and, on the other hand, a weakening of the DHPRα_1S/RyR1 orthograde signaling. Dysregulation of RyR1 activity of Triadin-null cells leads to enhanced SR Ca²⁺ leakage and subsequent reduction in SR Ca²⁺ content. In addition, lack of Triadin expression activates Ca²⁺ entry pathways that are both store-dependent and store-independent (sensitive to TRPC/Orai-1 inhibitors). Ca²⁺ entry and SR Ca²⁺ leakage could contribute independently to elevate myoplasmic [Ca²⁺]_rest.