Intravascular pressure stimulates functional Kv1.5 surface expression in mesenteric artery smooth muscle cells

Intravascular pressure stimulates arterial depolarization, leading to myocyte voltage‐dependent K + (K V ) channel activation that opposes the resulting vasoconstriction. We tested the hypothesis that membrane potential regulates K V channel surface expression to modulate mesenteric artery contractility. Q‐PCR indicated predominant expression of K V 1.5 and 2.1, with lower levels of 1.2 and 2.2 in mesenteric arteries. In isolated arteries at zero pressure, ~70% of total and surface K V 1.5 protein was lost in 3 hrs. Total or surface K V 2.1 protein did not change. K V 1.5 or 2.1 mRNA were also unchanged. Depolarization (30 mM K + ) prevented loss of K V 1.5 and this was blocked by nimodipine, a voltage‐dependent Ca 2+ channel blocker. Bafilomycin, a lysosome inhibitor, prevented K V 1.5 loss, and MG‐132, a proteasome inhibitor, inhibited loss by ~50% in non‐pressurized arteries. The functional significance of K V 1.5 surface expression was studied in arteries maintained at low (10 mmHg) or physiological (80 mmHg) pressure (3 hrs), with diameter regulation then measured at 80 mmHg. Vasoconstriction to psora‐4, a K V 1 inhibitor, or 4‐AP, a broad K V inhibitor, was larger in arteries maintained at physiological pressure than those at low pressure. Data indicate that intravascular pressure inhibits degradation of K V 1.5 channels and thus, maintains functional surface expression of these proteins in arterial myocytes. NHLBI/NIH