A volume-activated taurine channel in skate hepatocytes: membrane polarity and role of intracellular ATP

Abstract

Osmoregulation in isolated hepatocytes and perfused livers of the little skate (Raja erinacea), an osmoconforming marine elasmobranch, is mediated in part by the uptake or release of the intracellular osmolyte taurine. To further characterize the efflux mechanism, [14C]taurine release and Na(+)-independent uptake were assessed after cell swelling in hypotonic media containing 0.1-100 mM taurine. Rate coefficients for [14C]taurine uptake (0.016 +/- 0.002 min-1) and efflux (0.015 +/- 0.003 min-1) were similar and independent of extracellular taurine concentration, indicating that a taurine-permeable channel mediates the release of this amino acid after cell swelling. Volume-activated taurine uptake and efflux were both blocked by pretreatment with the metabolic inhibitors 2,4-dinitrophenol, antimycin A, and KCN plus iodoacetate, by the sulfhydryl-reactive compound N-ethylmaleimide and the transport inhibitor 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid. [14C]taurine release via this channel was immediately blocked if isotonicity was restored or a membrane-permeable metabolic inhibitor (0.5 mM 2,4-dinitrophenol) was added at different times after a hypotonic stimulus. Similar, although delayed, effects were noted with antimycin A and KCN plus iodoacetate. When isolated perfused skate livers were exposed to hypotonic stimuli, all of the taurine was released into the sinusoidal circulation, but not into bile, an effect that was also blocked by restoring isotonicity. These findings demonstrate that taurine efflux from skate hepatocytes after cell swelling is mediated by a channel. This channel is localized to the basolateral membrane and appears to require the continual presence of intracellular ATP for its function.(ABSTRACT TRUNCATED AT 250 WORDS)

Characterization of a swelling-activated anion conductance in homozygous typing cell hepatoma cells

“…Based on the apparent permeability of swelling-activated tude of currents increases in a concentration-dependent manner with increases in transmembrane osmolar differences, anion channels in other cell types to a broad range of organic substrates, 16,17,21 including glucose, uridine 21 and taurine, 16,19 with maximal values of Ç070 pA/pF at 080 mV. The presence of swelling-activated conductance(s) provides a dynamic and on the evidence for swelling-activated taurine efflux in liver cells, 12,24 the effect of cell swelling on taurine permeabil-mechanism for coupling changes in cell volume to hepatic ion transport. Under physiological conditions, the responsible ity was evaluated in HTC cells.…”

“…These latory volume decrease (RVD). [9][10][11][12] The ability to recover from studies of homozygous HTC hepatoma cells, a model cell swelling is a general property of mammalian cells, but the liver cell line, evaluate the relationship between cell volspecific mechanisms involved show substantial differences ume and membrane ion permeability, and assess the among different cell types. In liver, volume regulatory mechapossibility that cell swelling allows the efflux of the innisms appear to contribute importantly to many organ-level tracellular osmolite taurine through the opening of a functions, including bile acid secretion, bile formation, and conductive pathway.…”

“…[1][2][3][4] However, the intracellular accumulation of alanine, erinacea (skate) in an ATP-sensitive manner. 12 NPPB inhiband presumably of other solutes as well, imposes an osmotic its the response, but in contrast to mammalian cells, 16 the stress due to the accompanying influx of water and cell swell-effects appear to be related in part to an NPPB-induced deing. [5][6][7][8] At the cellular level, the adaptive response to increases crease in cellular adenosine triphosphate (ATP) concentrations.…”

Release of osmolytes from perfused rat liver on perivascular nerve stimulation: α-adrenergic control of osmolyte efflux from parenchymal and nonparenchymal liver cells

“…6, Table 1), as does hypo-osmotic cell swelling. [42][43][44] This is suggestive of an involvement of volume-sensitive anion channels in nerve stimulationdependent taurine efflux from the liver. A small K ϩ release has been shown to occur in the perfused rat liver during nerve stimulation or infusion of phenylephrine, 2 and it could be speculated that this net K ϩ release reflects a cell-volume regulatory ion movement by opening K ϩ channels 48 to counteract the increase of cell volume induced by nerve stimulation or phenylephrine.…”

“…When DIDS was withdrawn from the perfusion medium, the stimulatory capacity of nerve stimulation on taurine release was restored. In the intact perfused liver, taurine can be released upon hypo-osmotic swelling, 41,42 and swelling-activated taurine efflux has been shown to be DIDS-sensitive in flounder erythrocytes, 43 skate hepatocytes, 44 H4IIE cells, and the perfused liver. 42 The results therefore indicate the existence of a DIDS-sensitive (putative volume-regulated) taurine-efflux pathway, which is at least in part activated by cell swelling upon nerve or ␣-adrenergic stimulation.…”