AJP - Cell Physiology, Vol 271, Issue 5 C1565-C1573, Copyright © 1996 by American Physiological Society

ARTICLES

Expression of CFTR controls cAMP-dependent activation of epithelial K+ currents

G. Loussouarn, S. Demolombe, R. Mohammad-Panah, D. Escande and I. Baro
Laboratoire de Physiopathologie et de Pharmacologie Cellulaires et Moleculaires, Hopital G & R Laennec, Nantes, France.

The perforated-patch configuration of the patch-clamp technique was used to record whole cell currents from human epithelial CFPAC-1 cells defective for functional cystic fibrosis transmembrane conductance regulator (CFTR). In CFPAC-1 cells, adenosine 3',5'-cyclic monophosphate (cAMP) stimulation with forskolin (10 microM) plus 8-(4-chlorophenylthio)adenosine 3',5'-cyclic monophosphate (400 microM) activated neither Cl- nor K+ currents. In the same cells transfected with wild-type CFTR gene, cAMP stimulation produced activation of both Cl- and K+ currents. In Cl(-)-depleted medium (gluconate as a substitute), cAMP stimulation evoked a K+ current in CFTR-transfected but not in untransfected CFPAC-1 cells. This cAMP-evoked K+ current was the sum of two components: 1) a time-independent inwardly rectifying component, and 2) a slowly relaxing component activated at positive voltages. Increasing intracellular Ca2+ with ionomycin (1 microM) activated K+ currents in either transfected or untransfected cells. In transfected cells, blocking the CFTR conductance with high-concentration glibenclamide (100 microM) reduced the K+ current when activated by cAMP but not when activated by Ca2+. Pretreating CFTR-transfected cells for 48 h with interferon-gamma downregulated CFTR gene expression and reduced cAMP but not Ca2+ activation of the whole cell K+ current. From these results, we conclude that functional membrane CFTR protein influences activation by cAMP of epithelial K+ currents.

This article has been cited by other articles:

				R. Belfodil, H. Barriere, I. Rubera, M. Tauc, C. Poujeol, M. Bidet, and P. Poujeol CFTR-dependent and -independent swelling-activated K+ currents in primary cultures of mouse nephron Am J Physiol Renal Physiol, April 1, 2003; 284(4): F812 - F828. [Abstract] [Full Text] [PDF]

				K. Kunzelmann and M. Mall Electrolyte Transport in the Mammalian Colon: Mechanisms and Implications for Disease Physiol Rev, January 1, 2002; 82(1): 245 - 289. [Abstract] [Full Text] [PDF]

				H. Yeger, J. Pan, X. W. Fu, C. Bear, and E. Cutz Expression of CFTR and Cl{-} conductances in cells of pulmonary neuroepithelial bodies Am J Physiol Lung Cell Mol Physiol, September 1, 2001; 281(3): L713 - L721. [Abstract] [Full Text] [PDF]

				F. Potet, J. D. Scott, R. Mohammad-Panah, D. Escande, and I. Baro AKAP proteins anchor cAMP-dependent protein kinase to KvLQT1/IsK channel complex Am J Physiol Heart Circ Physiol, May 1, 2001; 280(5): H2038 - H2045. [Abstract] [Full Text] [PDF]

				D. Yoo, W. Lo, S. Goodman, W. Ali, C. Semrad, and M. Field Interferon-gamma downregulates ion transport in murine small intestine cultured in vitro Am J Physiol Gastrointest Liver Physiol, December 1, 2000; 279(6): G1323 - G1332. [Abstract] [Full Text] [PDF]

				A. ZSEMBERY, M. STRAZZABOSCO, and J. GRAF Ca2+-activated Cl- channels can substitute for CFTR in stimulation of pancreatic duct bicarbonate secretion FASEB J, November 1, 2000; 14(14): 2345 - 2356. [Abstract] [Full Text]

				E. M. SCHWIEBERT, D. J. BENOS, M. E. EGAN, M. J. STUTTS, and W. B. GUGGINO CFTR Is a Conductance Regulator as well as a Chloride Channel Physiol Rev, January 1, 1999; 79(1): 145 - 166. [Abstract] [Full Text] [PDF]

				R. Mohammad-Panah, S. Demolombe, D. Riochet, V. Leblais, G. Loussouarn, H. Pollard, I. Baro, and D. Escande Hyperexpression of recombinant CFTR in heterologous cells alters its physiological properties Am J Physiol Cell Physiol, February 1, 1998; 274(2): C310 - C318. [Abstract] [Full Text] [PDF]