CaV3.1 channels facilitate calcium wave generation and myogenic tone development in mouse mesenteric arteries

The arterial myogenic response to intraluminal pressure elicits constriction to maintain tissue perfusion. Smooth muscle [Ca 2+ ] is a key determinant of constriction, tied to L-type (Ca V 1.2) Ca 2+ channels. While important, other Ca 2+ channels, particularly T-type could contribute to pressure regulation within defined voltage ranges. This study examined the role of one T-type Ca 2+ channel (Ca V 3.1) using C57BL/6 wild type and Ca V 3.1 −/− mice. Patch-clamp electrophysiology, pressure myography, blood pressure and Ca 2+ imaging defined the Ca V 3.1 −/− phenotype relative to C57BL/6. Ca V 3.1 −/− mice had absent Ca V 3.1 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 2+ wave generation, asynchronous events of Ca 2+ release from the sarcoplasmic reticulum, insensitive to L-type Ca 2+ channel blockade (Nifedipine, 0.3 µM). Proximity ligation assay (PLA) confirmed IP 3 R1/Ca V 3.1 close physical association. IP 3 R blockade (2-APB, 50 µM or xestospongin C, 3 µM) in nifedipine-treated C57BL/6 arteries rendered a Ca V 3.1 −/− contractile phenotype. Findings indicate that Ca 2+ influx through Ca V 3.1 contributes to myogenic tone at hyperpolarized voltages through Ca 2+ -induced Ca 2+ release tied to the sarcoplasmic reticulum. This study helps establish Ca V 3.1 as a potential therapeutic target to control blood pressure.