Figure 1.

Representation of Ca²⁺ fluxes in the muscle fiber. Upon sarcolemmal depolarization reaching T-tubules (1), DHPRs undergo a conformational change that activates RyR1 channels and results in Ca²⁺ release from the SR (2). Ca²⁺ diffuses to the sarcomere where it initiates muscle contraction (3). Muscle relaxation takes place when Ca²⁺ is sequestered into the SR by SERCAs (4) or pumped out of the fiber by membrane channels (NCX, PMCA) (5). Cytosolic Ca²⁺ also binds CaM, which activates the Ca²⁺-dependent signaling pathways resulting in muscle gene regulation (6). Cytosolic Ca²⁺ also reaches mitochondria (7), where it stimulates metabolism and ATP synthesis required for muscle contraction and relaxation.