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

Autor: Michele Sweeney, Sharon S. McDaniel, Stefanie Krick, Jason X.-J. Yuan, Bethany R. Lapp, Oleksandr Platoshyn, Jian-Ying Wang, Vera A. Golovina, Victor A. Miriel, Ying Yu
Rok vydání: 2001
Předmět:
Zdroj: Journal of applied physiology (Bethesda, Md. : 1985). 91(5)
ISSN: 8750-7587
Popis: Activity of voltage-gated K+(Kv) channels controls membrane potential ( Em). Membrane depolarization due to blockade of K+channels in mesenteric artery smooth muscle cells (MASMC) should increase cytoplasmic free Ca2+concentration ([Ca2+]cyt) and cause vasoconstriction, which may subsequently reduce 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 of Kv channels and examined the role of Kv channel function in regulating Emin MASMC and intestinal epithelial cells (IEC). MASMC and IEC functionally expressed multiple Kv channel α- and β-subunits (Kv1.1, Kv1.2, Kv1.3, Kv1.4, Kv1.5, Kv2.1, Kv4.3, and Kv9.3, as well as Kvβ1.1, Kvβ2.1, and Kvβ3), 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 of 4-aminopyridine (4-AP), a Kv-channel blocker, reduced whole cell Kv currents and caused Emdepolarization in both MASMC and IEC. The 4-AP-induced Emdepolarization increased [Ca2+]cytin MASMC and caused mesenteric vasoconstriction. Furthermore, ingestion of 4-AP significantly reduced the weight gain in rats. These results suggest that MASMC and IEC express multiple Kv channel α- and β-subunits. The function of these Kv channels plays an important role in controlling Em. The membrane depolarization-mediated increase in [Ca2+]cytin MASMC and mesenteric vasoconstriction may inhibit transportation of absorbed nutrients via mesenteric circulation and limit weight gain.
Databáze: OpenAIRE