Anorexic effect of K+ channel blockade in mesenteric arterial smooth muscle and intestinal epithelial cells

Activity of voltage-gated K+ (Kv) channels controls membrane potential (E-m ). Membrane depolarization due to blockade of K+ channels in mesenteric art ery smooth muscle cells (MASMC) should increase cytoplasmic free Ca2+ conce ntration ([Ca2+](cyt)) and cause vasoconstriction, which may subsequently r educe the mesenteric blood flow and inhibit the transportation of absorbed nutrients to the liver and adipose tissue. In this study, we characterized and compared the electrophysiological properties and molecular identities o f Kv channels and examined the role of Kv channel function in regulating Em in MASMC and intestinal epithelial cells (IEC). MASMC and IEC functionally expressed multiple Kv channel alpha- and beta -subunits (Kv1.1, Kv1.2, Kv1 .3, Kv1.4, Kv1.5, Kv2.1, Kv4.3, and Kv9.3, as well as Kv beta1.1, Kv beta2. 1, and Kv beta3), but only MASMC expressed voltage-dependent Ca2+ channels. The current density and the activation and inactivation kinetics of whole cell Kv currents were similar in MASMC and IEC. Extracellular application o f 4-aminopyridine (4-AP), a Kv-channel blocker, reduced whole cell Kv curre nts and caused Em depolarization in both MASMC and IEC. The 4-AP-induced E- m depolarization increased [Ca2+](cyt) in MASMC and caused mesenteric vasoc onstriction. Furthermore, ingestion of 4-AP significantly reduced the weigh t gain in rats. These results suggest that MASMC and IEC express multiple K v channel alpha- and beta -subunits. The function of these Kv channels play s an important role in controlling E-m. The membrane depolarization-mediate d increase in [Ca2+](cyt) in MASMC and mesenteric vasoconstriction may inhi bit transportation of absorbed nutrients via mesenteric circulation and lim it weight gain.