AJP - Gastrointestinal and Liver Physiology, Vol 271, Issue 2 239-G248, Copyright © 1996 by American Physiological Society

ARTICLES

Regulation of cell volume in a human biliary cell line: activation of K+ and Cl- currents

R. M. Roman, Y. Wang and J. G. Fitz
Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA.

The mechanisms responsible for recovery from cell swelling were evaluated in Mz-ChA-1 cells from human cholangiocarcinoma, a model biliary cell line. Exposure to hypotonic buffer (40% less NaCl) rapidly increased relative cell volume to 1.35 +/- 0.10 as measured by a Coulter Multisizer, followed by regulatory volume decrease to 1.08 +/- 0.03 by 30 min. The same maneuver increased 86Rb (69 +/- 17%) and 125I (422 +/- 58%) efflux in cell monolayers. 86Rb efflux was selectively inhibited by Ba2+ [half-maximal inhibitory concentration (IC50) approximately 1.5 mM], and 125I by 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB) (IC60 approximately 50 microM). Inhibition of these conductive pathways partially inhibited recovery from swelling. Membrane conductance measured by whole cell patch-clamp analysis increased in 57 of 57 cells during swelling due to activation of both K+ and Cl- conductances in most cells. K+ currents (75% of cells, 881 +/- 150 pA at 0 mV) were nearly linear and Ba2+ sensitive; Cl- currents (70% of cells, 2,696 +/- 244 pA at +60 mV) were outwardly rectified, showed time-dependent inactivation at depolarizing potentials, and were inhibited by NPPB. Chelation of cytosolic Ca2+ decreased swelling-induced isotope efflux, prevented activation of macroscopic K+ and Cl- currents, and blocked volume recovery. These studies indicate that biliary cells are able to regulate cell volume during osmotic stress by activation of separate K+ and Cl- conductances through a mechanism that depends in part on Ca(2+)-sensitive signaling pathways.

This article has been cited by other articles:

				A. K. Dutta, K. Woo, R. B. Doctor, J. G. Fitz, and A. P. Feranchak Extracellular nucleotides stimulate Cl- currents in biliary epithelia through receptor-mediated IP3 and Ca2+ release Am J Physiol Gastrointest Liver Physiol, November 1, 2008; 295(5): G1004 - G1015. [Abstract] [Full Text] [PDF]

				F. Freudenberg, A. L. Broderick, B. B. Yu, M. R. Leonard, J. N. Glickman, and M. C. Carey Pathophysiological basis of liver disease in cystic fibrosis employing a {Delta}F508 mouse model Am J Physiol Gastrointest Liver Physiol, June 1, 2008; 294(6): G1411 - G1420. [Abstract] [Full Text] [PDF]

				K. Woo, A. K. Dutta, V. Patel, C. Kresge, and A. P. Feranchak Fluid flow induces mechanosensitive ATP release, calcium signalling and Cl- transport in biliary epithelial cells through a PKC{zeta}-dependent pathway J. Physiol., June 1, 2008; 586(11): 2779 - 2798. [Abstract] [Full Text] [PDF]

				B. Chen, G. Nicol, and W. K. Cho Electrophysiological characterization of volume-activated chloride currents in mouse cholangiocyte cell line Am J Physiol Gastrointest Liver Physiol, December 1, 2004; 287(6): G1158 - G1167. [Abstract] [Full Text] [PDF]

				G. Alpini, J. L. Phinizy, S. Glaser, H. Francis, A. Benedetti, L. Marucci, and G. LeSage Development and characterization of secretin-stimulated secretion of cultured rat cholangiocytes Am J Physiol Gastrointest Liver Physiol, June 1, 2003; 284(6): G1066 - G1073. [Abstract] [Full Text] [PDF]

				W. K. Cho Characterization of regulatory volume decrease in freshly isolated mouse cholangiocytes Am J Physiol Gastrointest Liver Physiol, December 1, 2002; 283(6): G1320 - G1327. [Abstract] [Full Text] [PDF]

				J. M. Fernandez-Fernandez, M. Nobles, A. Currid, E. Vazquez, and M. A. Valverde Maxi K+ channel mediates regulatory volume decrease response in a human bronchial epithelial cell line Am J Physiol Cell Physiol, December 1, 2002; 283(6): C1705 - C1714. [Abstract] [Full Text] [PDF]

				R. Roman, A. P. Feranchak, M. Troetsch, J. C. Dunkelberg, G. Kilic, T. Schlenker, J. Schaack, and J. G. Fitz Molecular characterization of volume-sensitive SKCa channels in human liver cell lines Am J Physiol Gastrointest Liver Physiol, January 1, 2002; 282(1): G116 - G122. [Abstract] [Full Text] [PDF]

				D. B. Shennan and M. Peaker Transport of Milk Constituents by the Mammary Gland Physiol Rev, July 1, 2000; 80(3): 925 - 951. [Abstract] [Full Text] [PDF]

				K. D. Salter, J. G. Fitz, and R. M. Roman Domain-specific purinergic signaling in polarized rat cholangiocytes Am J Physiol Gastrointest Liver Physiol, March 1, 2000; 278(3): G492 - G500. [Abstract] [Full Text] [PDF]

				A. P. Feranchak, R. M. Roman, R. B. Doctor, K. D. Salter, A. Toker, and J. G. Fitz The Lipid Products of Phosphoinositide 3-Kinase Contribute to Regulation of Cholangiocyte ATP and Chloride Transport J. Biol. Chem., October 22, 1999; 274(43): 30979 - 30986. [Abstract] [Full Text] [PDF]

				R. M. Roman, A. P. Feranchak, K. D. Salter, Y. Wang, and J. G. Fitz Endogenous ATP release regulates Cl- secretion in cultured human and rat biliary epithelial cells Am J Physiol Gastrointest Liver Physiol, June 1, 1999; 276(6): G1391 - G1400. [Abstract] [Full Text] [PDF]

				B. D. SCHULTZ, A. K. SINGH, D. C. DEVOR, and R. J. BRIDGES Pharmacology of CFTR Chloride Channel Activity Physiol Rev, January 1, 1999; 79(1): 109 - 144. [Abstract] [Full Text] [PDF]

				A. L. Taylor, B. A. Kudlow, K. L. Marrs, D. C. Gruenert, W. B. Guggino, and E. M. Schwiebert Bioluminescence detection of ATP release mechanisms in epithelia Am J Physiol Cell Physiol, November 1, 1998; 275(5): C1391 - C1406. [Abstract] [Full Text] [PDF]

				T. Schlenker, J. M.-J. Romac, A. I. Sharara, R. M. Roman, S. J. Kim, N. Larusso, R. A. Liddle, and J. G. Fitz Regulation of biliary secretion through apical purinergic receptors in cultured rat cholangiocytes Am J Physiol Gastrointest Liver Physiol, November 1, 1997; 273(5): G1108 - G1117. [Abstract] [Full Text] [PDF]

				R. M. Roman, Y. Wang, S. D. Lidofsky, A. P. Feranchak, N. Lomri, B. F. Scharschmidt, and J. G. Fitz Hepatocellular ATP-binding Cassette Protein Expression Enhances ATP Release and Autocrine Regulation of Cell Volume J. Biol. Chem., August 29, 1997; 272(35): 21970 - 21976. [Abstract] [Full Text] [PDF]

				G. M. Braunstein, R. M. Roman, J. P. Clancy, B. A. Kudlow, A. L. Taylor, V. Gh. Shylonsky, B. Jovov, K. Peter, T. Jilling, I. I. Ismailov, et al. Cystic Fibrosis Transmembrane Conductance Regulator Facilitates ATP Release by Stimulating a Separate ATP Release Channel for Autocrine Control of Cell Volume Regulation J. Biol. Chem., February 23, 2001; 276(9): 6621 - 6630. [Abstract] [Full Text] [PDF]