title: Swelling-activated K+ efflux and regulatory volume decrease efficiency in human bronchial epithelial cells.
abstract: This study describes the correlation between cell swelling-induced K+ efflux and volume regulation efficiency evaluated with agents known to modulate ion channel activity and/or intracellular signaling processes in a human bronchial epithelial cell line, 16HBE14o(-1). Cells on permeable filter supports, differentiated into polarized monolayers, were monitored continuously at room temperature for changes in cell height (T(c)), as an index of cell volume, whereas (86)Rb efflux was assessed for K+ channel activity. The sudden reduction in osmolality of both the apical and basolateral perfusates (from 290 to 170 mosmol/kg H(2)O) evoked a rapid increase in cell volume by 35%. Subsequently, the regulatory volume decrease (RVD) restored cell volume almost completely (to 94% of the isosmotic value). The basolateral (86)Rb efflux markedly increased during the hyposmotic shock, from 0.50 +/- 0.03 min(-1) to a peak value of 6.32 +/- 0.07 min(-1), while apical (86)Rb efflux was negligible. Channel blockers, such as GdCl(3) (0.5 mM), quinine (0.5 mM) and 5-nitro-2-(3-phenyl-propylamino) benzoic acid (NPPB, 100 microM), abolished the RVD. The protein tyrosine kinase inhibitors tyrphostin 23 (100 microM) and genistein (150 microM) attenuated the RVD. All agents decreased variably the hyposmosis-induced elevation in (86)Rb efflux, whereas NPPB induced a complete block, suggesting a link between basolateral K(+) and Cl(-1) efflux. Forskolin-mediated activation of adenylyl cyclase stimulated the RVD with a concomitant increase in basolateral (86)Rb efflux. These data suggest that the basolateral extrusion of K+ and Cl(-1) from 16HBE14o(-1) cells in response to cell swelling determines RVD efficiency.
authors.affiliation: Laboratory of Physiology, K. U. Leuven, Campus Gasthuisberg, B-3000 Leuven, Belgium.
authors.forename: Adrian
authors.initials: A
authors.lastname: Caplanusi
authors.forename: Kwang-Jin
authors.initials: KJ
authors.lastname: Kim
authors.forename: Els
authors.initials: E
authors.lastname: Lariviere
authors.forename: Willy
authors.initials: W
authors.lastname: Van Driessche
authors.forename: Danny
authors.initials: D
authors.lastname: Jans
mesh_terms: D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism; D001980:Bronchi / Q000166:cytology / Q000378:metabolism*; D002461:Cell Line, Transformed; D048429:Cell Size / Q000187:drug effects; D002712:Chlorides / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D017136:Ion Transport / Q000187:drug effects / Q000502:physiology; D009997:Osmotic Pressure / Q000187:drug effects; D011188:Potassium / Q000378:metabolism*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism*; D012414:Rubidium Radioisotopes / Q000494:pharmacology; D020032:Tyrphostins / Q000494:pharmacology
chemical_list: D000067956:Adenylyl Cyclase Inhibitors; D002712:Chlorides; D004791:Enzyme Inhibitors; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D012414:Rubidium Radioisotopes; D020032:Tyrphostins; D005576:Colforsin; D000262:Adenylyl Cyclases; C060641:tyrphostin A23; D011188:Potassium