Fig. 13.

Proposed myoendothelial feedback pathway. Smooth muscle agonists, such as phenylephrine, activate G protein-coupled receptors (GPCR) to initiate IP₃ production via phospholipase C (PLC). This second messenger crosses myoendothelial gap junctions and triggers Ca²⁺ release from IP₃Rs localized to the ER. As Ca²⁺ wavelets spread from the initiation site, they activate intermediate-conductance Ca²⁺-activated K⁺ (IK) channels concentrated within or near the endothelial projection. Resulting hyperpolarization spreads back to the smooth muscle layer, where it attenuates the initial depolarization. This reduces Ca²⁺ influx through voltage-gated Ca²⁺ (VGCC) channels and, consequently, moderates arterial constriction. SK, small-conductance Ca²⁺-activated K⁺ channel.