ATP regulation of a swelling-activated osmolyte channel in skate hepatocytes

Hypotonic swelling of isolated skate hepatocytes activates a regulatory volume decrease (RVD) which is achieved in part by the release of taurine and other intracellular organic osmolytes. Volume-activated taurine efflux appears to be mediated by an anion channel that exhibits a taurine/chloride permeability ratio of approximately 0.2. Of significance, this channel was shown to be regulated by intracellular nucleotide. When intracellular ATP was decreased to about 50% of control levels, channel opening was completely prevented. Many putative ion channel blockers were found to inhibit the channel indirectly, by depleting intracellular ATP, rather than by directly interacting with the channel. Investigators using these channel blockers in whole cell preparations should be aware of this alternative mechanism. Cell swelling-activated taurine efflux was also inhibited by HgCl2, DIDS, and pyridoxal 5-phosphate, at concentrations of these agents that had no effect on intracellular ATP levels, suggesting additional mechanisms of inhibition and regulation of the volume-sensitive osmolyte channels.