Myocardial Blood Flow Control by Oxygen Sensing Vascular Kvβ Proteins.
Title
Myocardial Blood Flow Control by Oxygen Sensing Vascular Kvβ Proteins.
Creator
Ohanyan V;Raph SM;Dwenger MM;Hu X;Pucci T;Mack GD;Moore IJB;Chilian WM;Bhatnagar A;Nystoriak MA
Publisher
Circulation Research
Date
2021
2021-01-27
Description
Rationale: Voltage-gated potassium (Kv) channels in vascular smooth muscle are essential for coupling myocardial blood flow (MBF) with the metabolic demand of the heart. These channels consist of a transmembrane pore domain that associates with auxiliary Kvβ1 and Kvβ2 proteins, which differentially regulate Kv function in excitable cells. Nonetheless, the physiological role of Kvβ proteins in regulating vascular tone and metabolic hyperemia in the heart remains unknown. Objective: To test the hypothesis that Kvβ proteins confer oxygen sensitivity to vascular tone and are required for regulating blood flow in the heart. Methods and Results: Mice lacking Kvβ2 subunits exhibited suppressed MBF, impaired cardiac contractile performance, and failed to maintain elevated arterial blood pressure in response to catecholamine-induced stress. In contrast, ablation of Kvβ1.1 reduced cardiac workload, modestly elevated MBF, and preserved cardiac function during stress compared with wild type mice. Coronary arteries isolated from Kvβ2-/-, but not Kvβ1.1-/-, mice, had severely blunted vasodilation to hypoxia when compared with arteries from wild type mice. Moreover, vasodilation of small diameter coronary and mesenteric arteries due to L-lactate, a biochemical marker of reduced tissue oxygenation and anaerobic metabolism, was significantly attenuated in vessels isolated from Kvβ2-/- mice. Inducible enhancement of the Kvβ1:Kvβ2 ratio in Kv1 channels of arterial smooth muscle abolished L-lactate-induced vasodilation and suppressed the relationship between MBF and cardiac workload.Conclusions: The Kvβ proteins differentially regulate vascular tone and myocardial blood flow, whereby Kvβ2 promotes and Kvβ1.1 inhibits oxygen-dependent vasodilation and augments blood flow upon heightened metabolic demand.
Subject
coronary arteris; microcirculation; myogenic tone; nicotinamide adenine dinucleotide; voltage-gated potassium channels
Identifier
Format
journalArticle
URL Address
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Rights
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
ISSN
1524-4571 0009-7330
NEOMED College
NEOMED College of Medicine
NEOMED Department
Department of Integrative Medical Sciences
Update Year & Number
February 2021 List
Citation
Ohanyan V;Raph SM;Dwenger MM;Hu X;Pucci T;Mack GD;Moore IJB;Chilian WM;Bhatnagar A;Nystoriak MA, “Myocardial Blood Flow Control by Oxygen Sensing Vascular Kvβ Proteins.,” NEOMED Bibliography Database, accessed June 15, 2025, https://neomed.omeka.net/items/show/11567.