title: Regulatory volume decrease in human esophageal epithelial cells.
abstract: In vivo human esophageal epithelial cells are regularly exposed to hyposmolal stress. This stress, however, only becomes destructive when the surface epithelial cell (barrier) layers are breached and there is contact of the hyposmolal solution with the basolateral cell membranes. The present investigation was designed to examine the effects of hyposmolal stress in the latter circumstance using as a model for human esophageal epithelial cells the noncancer-derived HET-1A cell line. Cell volume and the response to hyposmolal stress in suspensions of HET-1A cells were determined by cell passage through a Coulter Counter Multisizer II. HET-1A cells behaved as osmometers over the range of 280 to 118 mosmol/kg H(2)O with rapid increases in cell volume < or = 15-20% above baseline. Following swelling, the cells exhibited regulatory volume decrease (RVD), restoring baseline volume within 30 min, despite continued hyposmolal stress. With the use of pharmacologic agents and ion substitutions, RVD appeared to result from rapid activation of parallel K(+) and Cl(-) conductance pathways and this was subsequently joined by activation of a KCl cotransporter. Exposure to hyposmolal stress in an acidic environment, pH 6.6, inhibited, but did not abolish, RVD. These data indicate that human esophageal epithelial cells can protect against hyposmolal stress by RVD and that the redundancy in mechanisms may, to some extent, serve as added protection in patients with reflux disease when hyposmolal stress may occur in an acidic environment.
authors.affiliation: Department of Medicine, Tulane University School of Medicine and Veterans Administration Medical Center, New Orleans, Louisiana 70112 - 2699, USA. gorlando@tulane.edu
authors.forename: Geraldine S
authors.initials: GS
authors.lastname: Orlando
authors.forename: Nelia A
authors.initials: NA
authors.lastname: Tobey
authors.forename: Paul
authors.initials: P
authors.lastname: Wang
authors.forename: Solange
authors.initials: S
authors.lastname: Abdulnour-Nakhoul
authors.forename: Roy C
authors.initials: RC
authors.lastname: Orlando
mesh_terms: D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D002461:Cell Line, Transformed; D048429:Cell Size; D018118:Chloride Channels / Q000037:antagonists & inhibitors; D002712:Chlorides / Q000378:metabolism; D004553:Electric Conductivity; D004847:Epithelial Cells / Q000166:cytology; D004947:Esophagus / Q000166:cytology*; D006016:Glycolates / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007038:Hypotonic Solutions; D009994:Osmolar Concentration; D011188:Potassium / Q000378:metabolism; D026902:Potassium Channel Blockers; D027981:Symporters; D000096922:K Cl- Cotransporters
chemical_list: D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D018118:Chloride Channels; D002712:Chlorides; D006016:Glycolates; D007038:Hypotonic Solutions; D011188:Potassium; D026902:Potassium Channel Blockers; D027981:Symporters; D000096922:K Cl- Cotransporters; C015765:MK 473; C018564:dihydro-DIDS