Absence of Kv1.5 channels in vascular smooth muscle impaired metabolic dilation, resulting in lower myocardial blood flow, reduced tissue oxygen tension, and decreased ejection fraction during stress.
Kv1.5 channels in vascular smooth muscle are essential for coupling myocardial blood flow to cardiac metabolism, preventing cardiac pump dysfunction and tissue hypoxia during stress.
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 WT mice at baseline and all doses of norepinephrine), myocardial blood flow was lower in Kv1.5(-/-) mice than in WT mice. At high levels of cardiac work, tissue oxygen tension dropped significantly along with ejection fraction. Expression of Kv1.5 channels in smooth muscle in the null background rescued this phenotype of impaired metabolic dilation. In isolated vessels from Kv1.5(-/-) mice, relaxation to H2O2 was impaired, but responses to adenosine and acetylcholine were normal compared with those from WT mice. CONCLUSIONS: Kv1.5 channels in vascular smooth muscle play a critical role in coupling myocardial blood flow to cardiac metabolism. Absence of these channels disassociates metabolism from flow, resulting in cardiac pump dysfunction and tissue hypoxia.
Ohanyan et al. (2015) studied Coronary metabolic flow regulation. Kv1.5 channel absence (Kv1.5 null) vs. Wild-type mice was evaluated on Myocardial blood flow, tissue oxygen tension, and ejection fraction during cardiac stress. Absence of Kv1.5 channels in vascular smooth muscle impaired metabolic dilation, resulting in lower myocardial blood flow, reduced tissue oxygen tension, and decreased ejection fraction during stress.