Figure 3. Regulation of vascular smooth muscle cell (SMC) contractility by non-voltage-gated Ca²⁺ entry mechanisms.

(A) Activation of purinergic P2X receptor, TRPV4, TRPV1, TRPP1, TRPC3, and TRPC6 channels, and NCX in reverse mode increases SMC intracellular Ca²⁺, leading to vasoconstriction. (B) Ca²⁺ release from endolysosome via TRPML1 channel, or Ca²⁺ entry through TRPV4 channel at the plasma membrane activates ryanodine receptors (RyRs), triggering Ca²⁺ release signals (Ca²⁺ sparks) from the sarcoplasmic reticulum (SR). Ca²⁺ sparks activate large-conductance Ca²⁺-activated potassium (BK) channels. BK channels hyperpolarize the SMC membrane and cause vasodilation. Ca²⁺ release through IP3R induces SMC contraction. Sarco-endoplasmic reticulum Ca²⁺-ATPase (SERCA), by sequestering cytoplasmic Ca²⁺ back into the SR, maintains low cytosolic Ca²⁺ concentration. TRPV, TRPP, TRPC, TRPML, members of transient receptor potential channel family; NCX, Na⁺/Ca²⁺ exchanger.