Ca _v 3.1 Channels Modulate Ca _v 1.2 Functional Coupling: Implications to Myogenic Response

Introduction and Aim: Myogenic response is an autoregulatory arterial constriction to elevated blood pressure – a reflex essential for proper blood flow distribution. Historically, it’s mechanistic basis is explained as arterial depolarization opening voltage-gated Ca 2+ channels (VGCC), the primary subtype being L-type (Ca V 1.2). While unarguably important, additional regulatory mechanisms may exist including one where T-type (Ca V 3.1) Ca 2+ channels alone or in interaction with Ca V 1.2 play a facilitatory role in myogenic tone development. Methods: A detailed electrical analysis was completed using patch-clamp electrophysiology (whole-cell & cell-attached) on rodent cerebral arterial smooth muscle cells. Intracellular [Ca 2+ ] ([Ca 2+ ] i ) in resistant arteries was assessed using pressure myography and Fura-2AM. Results: Whole-cell patch-clamp revealed that pressure-like stimuli increased the Ca V 1.2, but not the Ca V 3.1 current. Single channel analysis tied the Ca V 1.2 activity rise to enhanced 1) functional coupling and 2) subunit trafficking to caveolae. Pressure-induced functional coupling was observed in intact arteries as manifested by elevated [Ca 2+ ] i (at 80 vs 20 mmHg) in the presence of 30 mM K + to standardize membrane potential (-40mV). To test the role of Ca V 3.1 in pressure-regulation of Ca V 1.2, single channel analysis was repeated in arterial myocytes from Ca V 3.1 −/− animals. Intriguingly, while pressure continued to foster Ca V 1.2 trafficking, it didn’t augment functional coupling. Likewise, we didn’t observe the elevated Ca 2+ response in arteries (at 80 vs 20 mmHg) when membrane potential was standardized. There was, however, evidence of higher baseline Ca V 1.2 activity in both experimental sets. Conclusions: Our results indicate that pressure increases Ca V 1.2 activity by enhancing perimembrane trafficking and functional coupling. We propose that the latter is tied to Ca V 3.1 and the induction of Ca 2+ -induced inactivation, an effect that partly dissipates as an artery depolarizes. The abolishment of Ca V 3.1 activity and thus the fine tuning of Ca V 1.2 functional coupling might facilitate arterial tone development in the hypertensive state. Supported by CIHR and Roraback Chair in Vascular Biology and Neuroscience. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.