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Significance Our data challenge the generally accepted view that Kv2.1 proteins regulate arterial smooth muscle function by regulating their membrane potential. Rather, we discovered that Kv2.1 plays both conductive and structural roles with opposing functional consequences on arterial myocytes, with the former predominating in males, the latter in females. Opening of Kv2.1 channels opposes vasoconstriction by inducing membrane hyperpolarization. In addition to this conductive function, Kv2.1 promotes the structural clustering of CaV 1.2 channels, thereby enhancing Ca2+ influx and inducing vasoconstriction. These two functions are highlighted by differences in the regulation of membrane potential, intracellular Ca2+ , and myogenic tone between males and females. Our data suggest that these disparities derive from sex-specific variations in Kv2.1 expression levels in male versus female myocytes.

Kv2.1 channels play opposing roles in regulating membrane potential, Ca 2+ channel function, and myogenic tone in arterial smooth muscle

Kv2.1 channels play opposing roles in regulating membrane potential, Ca ²⁺ channel function, and myogenic tone in arterial smooth muscle