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

Abstract

in volume includes the opening of ion efflux pathways to Liver cell volume and intracellular ion concentrations decrease the amount of intracellular ions. 6 Solute efflux leads are maintained within a narrow physiologic range by to recovery toward basal values, a process referred to as reguregulated changes in membrane ion permeability. 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. Cell swelling induced by exposure exocytosis. , and swelling has been shown to cause exposure to hypotonic solution or 2) intracellular perfuan increase in the partial membrane conductance to Cl 0 in sion with hypertonic sucrose-containing solutions actisome but not in all studies. 11,15 Thus, swelling-activated Cl 0 -vated an anion-selective current which was outwardly efflux could be due to the opening of anion channels or could rectified and showed time-dependent inactivation at debe driven by membrane hyperpolarization without a primary polarizing potentials. The current density at 080 mV inincrease in membrane Cl 0 conductance. depolarizing potentials, and are inhibited by the depletion of 1,587% { 172% of basal levels (P õ .05). Intracellular perintracellular adenosine triphosphate (ATP). [16][17][18] Cell swelling fusion with hypertonic solutions activated currents caralso stimulates the efflux of other organic solutes, including ried by anionic taurine, with an estimated taurine/Cl 0 taurine, a zwitterionic amino acid found in high concentrapermeability ratio of .88 { .17 for whole cell currents.tions in many cells including hepatocytes. 16,19,20 Swelling-actiThese studies demonstrate that the HTC membrane vated taurine efflux is inhibited by anion channel blockanion permeability is closely coupled to changes in cell ers, including 5-nitro-2-(3-phenylpropylamino)-benzoic acid volume, and that the recovery from swelling depends (NPPB), suggesting that both Cl 0 and taurine may leave the upon activation of anion-selective conductance pathcell through a common channel-mediated-mechanism. Recently, swelling-activated taurine efflux has been demHepatocytes show the facilitated uptake of a wide range of onstrated in several liver preparations. Using isotopic techorganic and inorganic solutes including bile acids, amino niques, hypotonic exposure has been shown to increase tauacids, and HCO 0 3 , which are essential for normal cell func-rine fluxes in hepatocytes from the elasmobranch Raja tion.1-4 However, the intra...

Compensatory role of inducible annexin A2 for impaired biliary epithelial anion-exchange activity of inflammatory cholangiopathy

“…Extracellular ATP causes rapid increase of the intracellular Ca 2 þ concentration and subsequent activation of membrane Cl À channels through purinergic receptors in the process of bile formation by cholangiocytes. [54][55][56][57] In the present study, we demonstrated the decrease of AE activity by the extracellular ATP and partial recovery of the AE activity by the induction of ANXA2. The phosphorylation status of the amino-acid residue of ANXA2 also modulates its binding affinity to the membrane.…”

Activation of protein kinase C? couples cell volume to membrane Cl? permeability in HTC hepatoma and Mz-ChA-1 cholangiocarcinoma cells

“…Volume recovery is dependent on channel-mediated Cl Ϫ efflux. 13,15 Addition of chelerythrine (25 µmol/L) to hypotonic buffer did not affect the magnitude of swelling, but completely prevented volume recovery in both cell types (Table 1, Fig. 6).…”

Phosphatidylinositol 3-Kinase Contributes to Cell Volume Regulation through Effects on ATP Release

“…Increases in HTC cell volume stimulated by uptake of alanine (29) or exposure to hypotonic buffer (30,31) are followed by ATP efflux, receptor activation, and opening of membrane Cl Ϫ channels (30,33). Cells were passaged at weekly intervals and maintained in HCO 3 Ϫ -containing minimal essential medium (Life Technologies, Inc.) supplemented with 10% heat-inactivated fetal bovine serum, L-glutamine (2 mM), penicillin (100 IU/ml), and streptomycin (100 g/ml) as described previously (34).…”