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Departments of Medicine and Physiology, Tulane University School of Medicine, and Veterans Administration Medical Center, New Orleans, Louisiana 70112 - 2699
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/kgH2O with rapid increases in cell volume
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.
hyposmolality; HET-1A cells; ion channels; KCl cotransport; Coulter Counter
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