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

Format

journalArticle

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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 April 17, 2021, https://neomed.omeka.net/items/show/11567.

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