Requisite Role of Kv1.5 Channels in Coronary Metabolic Dilation

Rationale:In the working heart, coronary blood flow is linked to the production of metabolites, which modulate tone of smooth muscle in a redox-dependent manner. Voltage-gated potassium channels (Kv), which play a role in controlling membrane potential in vascular smooth muscle, have certain members that are redox-sensitive. Objective:To determine the role of redox-sensitive Kv1.5 channels in coronary metabolic flow regulation. Methods and Results:In mice (wild-type [WT], Kv1.5 null [Kv1.5−/−], and Kv1.5−/− and WT with inducible, smooth muscle–specific expression of Kv1.5 channels), we measured mean arterial pressure, myocardial blood flow, myocardial tissue oxygen tension, and ejection fraction before and after inducing cardiac stress with norepinephrine. Cardiac work was estimated as the product of mean arterial pressure and heart rate. Isolated arteries were studied to establish whether genetic alterations modified vascular reactivity. Despite higher levels of cardiac work in the Kv1.5−/− mice (versus ...