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

• Published in: Journal of applied physiology (1985) 2001-11, Vol.91 (5), p.2322-2333
• Main Authors: McDaniel, Sharon S, Platoshyn, Oleksandr, Yu, Ying, Sweeney, Michele, Miriel, Victor A, Golovina, Vera A, Krick, Stefanie, Lapp, Bethany R, Wang, Jian-Ying, Yuan, Jason X.-J
• Format: Article
• Language: English
• Subjects: 4-Aminopyridine - pharmacology; Animals; Appetite Depressants - pharmacology; Biological and medical sciences; Body Weight - drug effects; Calcium - metabolism; Cells, Cultured; Digestive system; Electrophysiology; Epithelial Cells - drug effects; Epithelial Cells - ultrastructure; Fundamental and applied biological sciences. Psychology; Glucose; Intestine. Mesentery; Intestines - cytology; Intestines - drug effects; Intestines - ultrastructure; Isometric Contraction - drug effects; Membrane Potentials - drug effects; Membranes; Mesenteric Arteries - drug effects; Muscle, Smooth, Vascular - drug effects; Muscular system; Patch-Clamp Techniques; Potassium; Potassium Channel Blockers; Potassium Channels - genetics; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; Vertebrates: digestive system
• ISSN: 8750-7587; 1522-1601
• DOI: 10.1152/jappl.2001.91.5.2322

Department of Medicine, University of California School of Medicine, San Diego, California 92103; Department of Pharmacology and Therapeutics, University of Florida College of Medicine, Gainesville, Florida 32610; and Departments of Physiology and Surgery, University of Maryland School of Medicine, Baltimore, Maryland 21201 Activity of voltage-gated K + (Kv) channels controls membrane potential ( E m ). Membrane depolarization due to blockade of K + channels in mesenteric artery smooth muscle cells (MASMC) should increase cytoplasmic free Ca 2+ concentration ([Ca 2+ ] 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 E m in MASMC and intestinal epithelial cells (IEC). MASMC and IEC functionally expressed multiple Kv channel - and -subunits (Kv1.1, Kv1.2, Kv1.3, Kv1.4, Kv1.5, Kv2.1, Kv4.3, and Kv9.3, as well as Kv 1.1, Kv 2.1, and Kv 3), but only MASMC expressed voltage-dependent Ca 2+ 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 E m depolarization in both MASMC and IEC. The 4-AP-induced E m depolarization increased [Ca 2+ ] cyt in 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 - and -subunits. The function of these Kv channels plays an important role in controlling E m . The membrane depolarization-mediated increase in [Ca 2+ ] cyt in MASMC and mesenteric vasoconstriction may inhibit transportation of absorbed nutrients via mesenteric circulation and limit weight gain. voltage-gated potassium channel; membrane potential; sodium-dependent glucose symport * S. S. McDaniel and O. Platoshyn contributed equally to this work.