Distinct K+ conductive pathways are required for Cl- and K+ secretion across distal colonic epithelium

• Published in: American Journal of Physiology: Cell Physiology Vol. 291; no. 4; pp. C636 - C648
• Main Authors: Halm, Susan Troutman, Liao, Tianjiang, Halm, Dan R
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.10.2006
• Subjects: Animals; Benzimidazoles - pharmacology; Carbachol - pharmacology; Cellular biology; Chlorides - antagonists & inhibitors; Chlorides - metabolism; Cholinergic Agonists - pharmacology; Colon; Colon - metabolism; Dinoprostone - pharmacology; Dose-Response Relationship, Drug; Drug Synergism; Electric Conductivity; Female; Guinea Pigs; Intermediate-Conductance Calcium-Activated Potassium Channels - metabolism; Intestinal Mucosa - metabolism; Male; Membranes; Osmolar Concentration; Potassium - antagonists & inhibitors; Potassium - metabolism; Potassium Channel Blockers - administration & dosage; Potassium Channel Blockers - pharmacology; Potassium Channels - drug effects; Potassium Channels - physiology; Pyrazoles - administration & dosage; Pyrazoles - pharmacology; Quaternary Ammonium Compounds - pharmacology; Rats; Rats, Sprague-Dawley; Studies; Tissue Distribution
• ISSN: 0363-6143; 1522-1563
• DOI: 10.1152/ajpcell.00557.2005

Department of Neuroscience, Cell Biology, and Physiology, Wright State University Boonshoft School of Medicine, Dayton, Ohio Submitted 31 October 2005 ; accepted in final form 1 April 2006 Secretion of Cl – and K + in the colonic epithelium operates through a cellular mechanism requiring K + channels in the basolateral and apical membranes. Transepithelial current [short-circuit current ( I sc )] and conductance ( G t ) were measured for isolated distal colonic mucosa during secretory activation by epinephrine (Epi) or PGE 2 and synergistically by PGE 2 and carbachol (PGE 2 + CCh). TRAM-34 at 0.5 µM, an inhibitor of K Ca 3.1 (IK, Kcnn4 ) K + channels (H. Wulff, M. J. Miller, W. Hänsel, S. Grissmer, M. D. Cahalan, and K. G. Chandy. Proc Natl Acad Sci USA 97: 8151–8156, 2000), did not alter secretory I sc or G t in guinea pig or rat colon. The presence of K Ca 3.1 in the mucosa was confirmed by immunoblot and immunofluorescence detection. At 100 µM, TRAM-34 inhibited I sc and G t activated by Epi ( 4%), PGE 2 ( 30%) and PGE 2 + CCh ( 60%). The IC 50 of 4.0 µM implicated involvement of K + channels other than K Ca 3.1. The secretory responses augmented by the K + channel opener 1-EBIO were inhibited only at a high concentration of TRAM-34, suggesting further that K Ca 3.1 was not involved. Sensitivity of the synergistic response (PGE 2 + CCh) to a high concentration TRAM-34 supported a requirement for multiple K + conductive pathways in secretion. Clofilium (100 µM), a quaternary ammonium, inhibited Cl – secretory I sc and G t activated by PGE 2 ( 20%) but not K + secretion activated by Epi. Thus Cl – secretion activated by physiological secretagogues occurred without apparent activity of K Ca 3.1 channels but was dependent on other types of K + channels sensitive to high concentrations of TRAM-34 and/or clofilium. epinephrine; prostaglandin E 2 ; cholinergic; Kcnn4 ; TRAM-34; clofilium Address for reprint requests and other correspondence: D. R. Halm, Dept. of Neuroscience, Cell Biology, and Physiology, Wright State Univ. Boonshoft School of Medicine, 3640 Colonel Glenn Hwy., Dayton, OH 45435 (e-mail: dan.halm{at}wright.edu )