Potassium channels in the peripheral microcirculation

Vascular smooth muscle (VSM) cells, endothelial cells (EC), and pericytes that form the walls of vessels in the microcirculation express a diverse array of ion channels that play an important role in the function of these cells and the microcirculation in both health and disease. This brief review focuses on the K+ channels expressed in smooth muscle and endothelial cells in arterioles. Microvascular VSM cells express at least four different classes of K+ channels, including inward-rectifier K+ channels (KIR), ATP-sensitive K+ channels (K-ATP), voltage-gated K+ channels (KY)., and large conductance Ca2+-activated K+ charmels (BKCa). VSM K-IR participate in dilation induced by elevated extracellular K+ and may also be activated by C-type natriuretic peptide, a putative endothelium-derived hyperpolarizing factor (EDHF). Vasodilators acting through cAMP or cGMP signaling pathways in ITSM may open K-ATP, K-V, and BKCa, causing membrane hyperpolarization and vasodilation. VSM BKCa, may also be activated by epoxides of arachidonic acid (EETs) identified as EDHF in some systems. conversely, vasoconstrictors may close K-ATP, K-V, and BKCa through protein kinase C., Rho-kinase, or c-Src pathways and contribute to VSM depolarization and vasoconstriction. At the same time K-V and BKCa act in a negative feedback manner to limit depolarization and prevent vasospasm. Microvascular EC express at least 5 classes of K+ channels, including small (sK(Ca)) and intermediate (IKCa) conductance Ca2+-activated K+ channels, K-IR, K-ATP, and K-V. Both sK and lK are opened by endothelium-dependent vasodilators that increase EC intracellular Ca2+ to cause membrane hyperpolarization that may be conducted through myoendothelial gap junctions to byperpolarize and relax arteriolar VSM. K-IR may serve to amplify sK(Ca)- and IKCa-induced hyperpolarization and allow, active transmission of hyperpolarization along EC through gap junctions. EC KIR channels may also be opened by elevated extracellular K+ and participate in K+-induced vasodilation. EC K-ATP channels may be activated by vasodilators as in VSM. KV channels may provide a negative feedback mechanism to limit depolarizatiou in some endothelial cells.