Activation of Smooth Muscle Kir2.1 Channels and Na+/K+ ATPase Mediates Dilation of Porcine Coronary Arterioles to Potassium

Metabolic stress on the heart can cause dilation of coronary arterioles for blood flow recruitment. Although potassium ions (K+) released from the myocardium are a major mediator for this response, the underlying signaling pathways for vasodilation are incompletely understood. Herein, roles of smooth muscle inward-rectifier K+ channel subtype 2.1 (Kir2.1) and Na+/K+ ATPase were examined. Porcine coronary arterioles were isolated, cannulated, and pressurized for vasomotor study. Vessels developed basal tone and dilated concentration-dependently to extraluminal K+ from 7 to 20 mM. Higher K+ concentrations (25-40 mM) caused graded vasoconstriction. Vasodilation to K+ (10 mM) was not altered by endothelial removal, and blockade of ATP-sensitive K+ channels, voltage-sensitive K+ channels, or calcium-activated K+ channels did not affect K+-induced vasodilation. However, sustained but not abrupt transient vasodilation to K+ was reduced by nonspecific Kir channel inhibitor Ba2+ or specific Kir2.1 channel blocker chloroethylclonidine. The Na+/K+ ATPase inhibitor ouabain attenuated K+-elicited vasodilation, and ouabain with Ba2+ abolished the response. Transfection of arterioles with Kir2.1 antisense oligonucleotides abolished sustained but not transient dilation. It is concluded that extraluminal K+ elevation within the physiological range induces initial transient dilation of porcine coronary arterioles by activating Na+/K+ ATPase and sustained dilation via smooth muscle Kir2.1 channels.