Role of Ca V 3.1 Channels in Myogenic Tone and Blood Pressure Regulation in Mouse Mesenteric Arteries

The myogenic response is a fundamental mechanism whereby intraluminal pressure elicits arterial constriction pursuant to maintenance of tissue perfusion. Smooth muscle [Ca 2+ ] is a key determinant of constriction, a process intimately tied to L‐type (Ca V 1.2) Ca 2+ channel activity. While important, other Ca 2+ channels are expressed and could contribute to pressure regulation within defined voltage ranges. In this regard, this study examined the role of T‐type Ca 2+ channels, using mesenteric arterioles from wild type (WT) and Ca V 3.1 ‐/‐ mice. Using pressure myography, experiments first revealed that Ca V 3.1 ‐/‐ arterioles displayed decidedly less myogenic tone than WT, particular at lower pressures (20 – 60 mmHg) where membrane potential is hyperpolarized. We next showed with rapid Ca 2+ imaging that reduced myogenic tone in Ca V 3.1 ‐/‐ arteries resulted from diminished Ca 2+ waves generation, asynchronous events dependent upon Ca 2+ release from the sarcoplasmic reticulum. In contrast, blockade of L‐type Ca 2+ channels with nifedipine (200 nM) had no effect on Ca 2+ waves, akin to previous findings. The proximity ligation assay confirmed a close association (<40 nm) between IP 3 R and Ca V 3.1, in WT and not knockout arterioles. In whole animals, this diminishment of myogenic tone coincided with a reduction in systemic blood pressure at rest. Intriguingly, this hypotension response did not impact blood pressure response to chronic AngII infusion. Taken together, this data suggests that Ca V 3.1 channels are contributors to tone development at low intraluminal pressures and that this effect is indirect through a Ca 2+ ‐induced Ca 2+ release mechanism involving the sarcoplasmic reticulum. Further experiments are being extended to define the role of Ca V 3.1 in other pathophysiological models.