Increased vascular CaV1.2 channel function enhances arterial tone in hypertension via angiotensin II/protein kinase C signaling, but the mechanisms are unclear. We hypothesize that phosphorylation of the α1C subunit at serine 1928 (S1928) mediates increased channel function and vascular reactivity during angiotensin II signaling and hypertension. Methods and Results: Using mesenteric arteries and arterial myocytes from control and angiotensin IIinfused mice, we employed imaging, electrophysiology, and physiological assays. Angiotensin II caused redistribution of α1C into larger clusters, correlating with increased CaV1.2 activity, intracellular Ca²⁺, myocyte contraction, myogenic tone, and altered blood flow in wild-type mice. These effects were prevented in S1928A knockin mice, where S1928 is mutated to alanine. In angiotensin II-induced hypertension, increases in α1C clustering, CaV1.2 activity, myogenic tone, and blood pressure observed in wild-type mice were reduced in S1928A mice. Conclusions: Phosphorylation of α1C at S1928 is essential for regulating channel distribution, activity, and vascular function during angiotensin II signaling and hypertension. Targeting this site may offer a therapeutic strategy for hypertension.

Victor Flores is a cardiovascular scientist who earned his Ph.D. from the Center for Research and Advanced Studies of the National Polytechnic Institute (CINVESTAV) in Mexico. He conducted postdoctoral research at the University of California, Davis, and was awarded a prestigious Fulbright fellowship at the University of Wisconsin, Madison. There, he led groundbreaking studies in cardiovascular pharmacology and calcium signaling. Recognized with multiple awards, including an NIH postdoctoral fellowship and the Fulbright award, Dr. Flores's work reflects his commitment to advancing cardiovascular health. As an active member of the American Physiological Society and SACNAS, he is devoted to promoting diversity and scientific excellence in the research community through peer mentorship and evaluation roles.