Activation of Smooth Muscle Kir2.1 Channels and Na+/K+-ATPase Mediates Dilation of Porcine Coronary Arterioles at Physiological Levels of 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, the 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 the nonspecific Kir channel inhibitor Ba2+ or 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 smooth muscle Na+/K+-ATPase and sustained dilation via smooth muscle Kir2.1 channels.