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Organic osmolyte and halide permeability pathways activated in epithelial HeLa cells by cell swelling were studied by radiotracer efflux techniques and single-cell volume measurements. The replacement of extracellular Cl−by anions that are more permeant through the volume-activated Cl−channel, as indicated by electrophysiological measurements, significantly decreased taurine efflux. In the presence of less-permeant anions, an increase in taurine efflux was observed. Simultaneous measurement of the125I, used as a tracer for Cl−, and [3H]taurine efflux showed that the time courses for the two effluxes differed. In Cl−-rich medium the increase in I−efflux was transient, whereas that for taurine was sustained. Osmosensitive Cl−conductance, assessed by measuring changes in cell volume, increased rapidly after hypotonic shock. The influx of taurine was able to counteract Cl−conductance-dependent cell shrinkage but only ∼4 min after triggering cell swelling. This taurine-induced effect was blocked by DIDS. Differences in anion sensitivity, the time course of activation, and sensitivity to DIDS suggest that the main cell swelling-activated permeability pathways for taurine and Cl−are separate.

Volume regulation is a property common to many animal cell types (for references, see reviews1, 2) and when exposed to anisotonic media they modify their intracellular concentration of osmolytes by activation of permeability pathways, leading to osmotically-driven water shifts. In response to swelling induced by hypotonicity, cells lose KC1 and organic osmolytes to recover their normal volume, a process known as regulatory volume decrease (RVD).