Shaker‐related voltage‐gated K⁺ channel expression and vasomotor function in human coronary resistance arteries

Objectives K V channels are important regulators of vascular tone, but the identity of specific K V channels involved and their regulation in disease remain less well understood. We determined the expression of K V 1 channel subunits and their role in cAMP ‐mediated dilation in coronary resistance arteries from subjects with and without CAD . Methods HCA s from patients with and without CAD were assessed for mRNA and protein expression of K V 1 channel subunits with molecular techniques and for vasodilator response with isolated arterial myography. Results Assays of mRNA transcripts, membrane protein expression, and vascular cell‐specific localization revealed abundant expression of K V 1.5 in vascular smooth muscle cells of non‐ CAD HCA s. Isoproterenol and forskolin, two distinct cAMP ‐mediated vasodilators, induced potent dilation of non‐ CAD arterioles, which was inhibited by both the general K V blocker 4‐ AP and the selective K V 1.5 blocker DPO ‐1. The cAMP ‐mediated dilation was reduced in CAD and was accompanied by a loss of or reduced contribution of 4‐ AP ‐sensitive K V channels. Conclusions K V 1.5, as a major 4‐ AP ‐sensitive K V 1 channel expressed in coronary VSMC s, mediates cAMP ‐mediated dilation in non‐ CAD arterioles. The cAMP ‐mediated dilation is reduced in CAD coronary arterioles, which is associated with impaired 4‐ AP ‐sensitive K V channel function.