Scaffolding builds to reduce blood pressure

Endothelial cells provide vasodilator signals to reduce blood pressure. In the small resistance arteries and arterioles, which determine the distribution and pressure of blood, the major signal is hyperpolarization reflecting the endothelial activity of calcium-activated potassium channels (K_Ca). In this issue of Science Signaling, Sonkusare et al. report that the scaffold protein AKAP150 is required for the kinase PKC and the calcium channel TRPV4 to enable receptor-mediated relaxation signaling. This scaffold enhances TRPV4 gating cooperativity and markedly amplifies the Ca²⁺signal, which ultimately activates (mainly) IK_Cachannels. Normally restricted to tiny endothelial projections, AKAP150 localization and associated signaling is disrupted in a model of hypertension, thereby diminishing hyperpolarization and vasodilation.