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

Richard M. Roman, Yu Wang, J. Gregory Fitz

Research output: Contribution to journalArticle

64 Scopus citations

Abstract

The mechanisms responsible for recovery from cell swelling were evaluated in M(z)-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%) effiux in cell monolayers. 86Rb effiux was selectively inhibited by Ba2+ [half-maximal inhibitory concentration (IC50) ~1.5 mM], and 125I by 5-nitro-2-(3- phenylpropylamino)-benzoic acid (NPPB) (IC50 ≃ 50 μM). 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 swellinginduced isotope effiux, 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 Ca2+-sensitive signaling pathways.

Original languageEnglish (US)
Pages (from-to)G239-G248
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume271
Issue number2 34-2
DOIs
StatePublished - Aug 1996

Keywords

  • bile duct epithelial cell
  • cell swelling
  • ion channel
  • patch clamp

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

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