AJP - Lung Cellular and Molecular Physiology, Vol 265, Issue 2 170-L177, Copyright © 1993 by American Physiological Society

ARTICLES

Calcium-dependent chloride secretion across cultures of human tracheal surface epithelium and glands

M. Yamaya, T. Ohrui, W. E. Finkbeiner and J. H. Widdicombe
Cystic Fibrosis Research Center, University of California, San Francisco 94143.

Surface epithelium and gland cells from human trachea were cultured on porous-bottom inserts and loaded with fura 2 to permit measurement of the intracellular calcium concentration ([Ca2+]i). Short-circuit current (Isc), an index of transepithelial active ion transport, was measured on cells from the same cultures. Surface epithelial [Ca2+]i of 82 +/- 15 nM was increased transiently by isoproterenol, histamine, and bradykinin with maximal increases of 88 +/- 17, 480 +/- 149, and 978 +/- 214 nM (n = 15), respectively. Baseline [Ca2+]i in cultured gland cells of 68 +/- 11 nM was increased transiently by isoproterenol, histamine, methacholine, and bradykinin with maximal increases of 105 +/- 19, 233 +/- 47, 327 +/- 121, and 634 +/- 151 nM (n = 17-21), respectively. In both cell types, mediators that increased [Ca2+]i also increased Isc with a time course identical to the increase in [Ca2+]i. Pretreatment with the calcium chelator, 1,2-bis-(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid, acetoxymethyl ester (BAPTA-AM), had no effect on basal Isc or transepithelial resistance but markedly inhibited both the Isc and [Ca2+]i responses to agonists. Forskolin (10(-5) M), 3-isobutyl-1-methylxanthine (10(-3) M), dibutyryl adenosine 3',5'-cyclic monophosphate (10(-3) M), and 8-(4-chlorophenylthio)-cAMP (10(-3) M) had no or only trivial effects on Isc and [Ca2+]i. We suggest that mediators increase Isc across human airway epithelium by activating Ca-dependent basolateral K channels, resulting in hyperpolarization and an increased driving force for Cl exit through apical membrane Cl channels.

This article has been cited by other articles:

				S. K. Inglis, S. G. Brown, M. J. Constable, N. McTavish, R. E. Olver, and S. M. Wilson A Ba2+-resistant, acid-sensitive K+ conductance in Na+-absorbing H441 human airway epithelial cells Am J Physiol Lung Cell Mol Physiol, May 1, 2007; 292(5): L1304 - L1312. [Abstract] [Full Text] [PDF]

				T. Irokawa, M. E. Krouse, N. S. Joo, J. V. Wu, and J. J. Wine A "virtual gland" method for quantifying epithelial fluid secretion Am J Physiol Lung Cell Mol Physiol, October 1, 2004; 287(4): L784 - L793. [Abstract] [Full Text] [PDF]

				A. S. Verkman, Y. Song, and J. R. Thiagarajah Role of airway surface liquid and submucosal glands in cystic fibrosis lung disease Am J Physiol Cell Physiol, January 1, 2003; 284(1): C2 - C15. [Abstract] [Full Text] [PDF]

				D. C. Devor and J. M. Pilewski UTP inhibits Na+ absorption in wild-type and Delta F508 CFTR-expressing human bronchial epithelia Am J Physiol Cell Physiol, April 1, 1999; 276(4): C827 - C837. [Abstract] [Full Text] [PDF]

				S. N. Uyekubo, H. Fischer, A. Maminishkis, B. Illek, S. S. Miller, and J. H. Widdicombe cAMP-dependent absorption of chloride across airway epithelium Am J Physiol Lung Cell Mol Physiol, December 1, 1998; 275(6): L1219 - L1227. [Abstract] [Full Text] [PDF]

				S. Moon, M. Singh, M. E. Krouse, and J. J. Wine Calcium-stimulated Cl- secretion in Calu-3 human airway cells requires CFTR Am J Physiol Lung Cell Mol Physiol, December 1, 1997; 273(6): L1208 - L1219. [Abstract] [Full Text] [PDF]