Gβγ subunit activation of K V 7 and BK Ca channels underlies calcitonin gene‐related peptide vasorelaxation in myogenic rat coronary resistance arteries
Year: 2026
Type: article
Abstract: Background and Purpose CGRP is a potent, clinically relevant coronary vasodilator known to play a role in cardioprotection. Here, we investigated the precise intracellular signalling pathways leading to vasodilation in small coronary arteries. Experimental Approach This study used ex vivo myography and intracellular recording techniques to investigate α‐CGRP‐induced vasorelaxation and vascular smooth muscle cell (VSMC) hyperpolarization in myogenically active rat isolated coronary arteries. Key Results CGRP‐induced vasorelaxation was not dependent on the endothelium, but relied heavily on K + channel activation. Immunohistochemistry indicated K V 7 and BK Ca channel expression in VSMC and endothelial cells. A combination of the K V 7 channel inhibitor, linopirdine and the BK Ca channel inhibitor, paxilline, significantly attenuated CGRP‐induced vasorelaxation in endothelium‐intact or denuded arteries. Electrophysiology confirmed that CGRP caused hyperpolarization and showed this was prevented by linopirdine and paxilline, also demonstrating a role for K V 7 and BK Ca channels in suppressing depolarizing smooth muscle spikes. These spikes were also suppressed by NO• and HNO donors, resulting in hyperpolarization. Gβγ subunit inhibition with gallein markedly right‐shifted CGRP‐induced vasorelaxation in both endothelium‐intact and denuded coronary arteries. Conclusion and Implications α‐CGRP stimulates robust vasorelaxation in the coronary microvasculature that relies on Gβγ subunit‐activated VSMC hyperpolarization involving K V 7 and BK Ca channels. These data enhance understanding of coronary microvascular physiology and inform the design of future therapeutic strategies targeting coronary vascular dysfunction.
Source: British Journal of Pharmacology
DOI: 10.1111/bph.70492
Institution: University of Oxford
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,780
Funder: British Heart Foundation
Awards: Endothelium-dependent actions of CGRP during ischaemic heart disease, Mechanisms of human coronary microvascular reactivity in ischaemic heart disease, G5113577447, TRPV4 channels in the feedback control of coronary artery myogenic tone, intake 2018 – PhD Studentship Ms Faseeha Ayaz; Ms Laura Chaffey; Donovan; Ms Yasemin-Xiomara Zurke
OpenAlex ID: W7161712239