Shaker-related Voltage-gated K Channel Expression and Vasomotor Function in Human Coronary Resistance Arteries

Objectives: K channels are important regulators of vascular tone, but the identity of specific K channels involved and their regulation in disease remain less well understood. We determined the expression of K 1 channel subunits and their role in cAMP-mediated dilation in coronary resistance arteries from subjects with and without CAD.

Methods: HCAs from patients with and without CAD were assessed for mRNA and protein expression of K 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 1.5 in vascular smooth muscle cells of non-CAD HCAs. Isoproterenol and forskolin, two distinct cAMP-mediated vasodilators, induced potent dilation of non-CAD arterioles, which was inhibited by both the general K blocker 4-AP and the selective K 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 channels.

Conclusions: K 1.5, as a major 4-AP-sensitive K 1 channel expressed in coronary VSMCs, 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 channel function.