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

Abstract

Intravascular pressure stimulates arterial depolarization, leading to myocyte voltage‐dependent K+ (KV) channel activation that opposes the resulting vasoconstriction. We tested the hypothesis that membrane potential regulates KV channel surface expression to modulate mesenteric artery contractility. Q‐PCR indicated predominant expression of KV1.5 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 KV1.5 protein was lost in 3 hrs. Total or surface KV2.1 protein did not change. KV1.5 or 2.1 mRNA were also unchanged. Depolarization (30 mM K+) prevented loss of KV1.5 and this was blocked by nimodipine, a voltage‐dependent Ca2+ channel blocker. Bafilomycin, a lysosome inhibitor, prevented KV1.5 loss, and MG‐132, a proteasome inhibitor, inhibited loss by ~50% in non‐pressurized arteries. The functional significance of KV1.5 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 KV1 inhibitor, or 4‐AP, a broad KV inhibitor, was larger in arteries maintained at physiological pressure than those at low pressure. Data indicate that intravascular pressure inhibits degradation of KV1.5 channels and thus, maintains functional surface expression of these proteins in arterial myocytes. NHLBI/NIH