%0 Journal Article
%A El-Lakany, Mohammed A
%A Haghbin, Nadia
%A Arora, Naman
%A Hashad, Ahmed M
%A Mironova, Galina Yu
%A Sancho González, María
%A Gros, Robert
%A Welsh, Donald G
%T Ca3.1 channels facilitate calcium wave generation and myogenic tone development in mouse mesenteric arteries.
%D 2023
%@ 2045-2322
%U https://hdl.handle.net/20.500.14352/134614
%X The arterial myogenic response to intraluminal pressure elicits constriction to maintain tissue perfusion. Smooth muscle [Ca] is a key determinant of constriction, tied to L-type (Ca1.2) Ca channels. While important, other Ca channels, particularly T-type could contribute to pressure regulation within defined voltage ranges. This study examined the role of one T-type Ca channel (Ca3.1) using C57BL/6 wild type and Ca3.1 mice. Patch-clamp electrophysiology, pressure myography, blood pressure and Ca imaging defined the Ca3.1 phenotype relative to C57BL/6. Ca3.1 mice had absent Ca3.1 expression and whole-cell current, coinciding with lower blood pressure and reduced mesenteric artery myogenic tone, particularly at lower pressures (20-60 mmHg) where membrane potential is hyperpolarized. This reduction coincided with diminished Ca wave generation, asynchronous events of Ca release from the sarcoplasmic reticulum, insensitive to L-type Ca channel blockade (Nifedipine, 0.3 µM). Proximity ligation assay (PLA) confirmed IPR1/Ca3.1 close physical association. IPR blockade (2-APB, 50 µM or xestospongin C, 3 µM) in nifedipine-treated C57BL/6 arteries rendered a Ca3.1 contractile phenotype. Findings indicate that Ca influx through Ca3.1 contributes to myogenic tone at hyperpolarized voltages through Ca-induced Ca release tied to the sarcoplasmic reticulum. This study helps establish Ca3.1 as a potential therapeutic target to control blood pressure.
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