title: Autocrine signaling through ATP release represents a novel mechanism for cell volume regulation.
abstract: Recovery of cell volume in response to osmotic stress is mediated in part by increases in the Cl- permeability of the plasma membrane. These studies evaluate the hypothesis that ATP release and autocrine stimulation of purinergic (P2) receptors couple increases in cell volume to opening of Cl- channels. In HTC rat hepatoma cells, swelling induced by hypotonic exposure increased membrane Cl- current density to 44.8 +/- 7.1 pA/pF at -80 mV. Both the rate of volume recovery and the increase in Cl- permeability were inhibited in the presence of the ATP hydrolase apyrase (3 units/ml) or by exposure to the P2 receptor blockers suramin and Reactive Blue 2 (10-100 microM). Cell swelling also stimulated release of ATP. Hypotonic exposure increased the concentration of ATP in the effluent of perfused cells by 170 +/- 36 nM in the presence of a nucleotidase inhibitor (P < 0.01). In whole-cell recordings with ATP as the charge carrier, cell swelling increased membrane current density approximately 30-fold to 16.5 +/- 10.4 pA/pF. These findings indicate that increases in cell volume lead to efflux of ATP through opening of a conductive pathway consistent with a channel, and that extracellular ATP is required for recovery from swelling. ATP may function as an autocrine factor that couples increases in cell volume to opening of Cl- channels through stimulation of P2 receptors.
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: R
authors.initials: R
authors.lastname: Roman
authors.forename: S D
authors.initials: SD
authors.lastname: Lidofsky
authors.forename: J G
authors.initials: JG
authors.lastname: Fitz
mesh_terms: D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001081:Apyrase / Q000494:pharmacology; D002462:Cell Membrane / Q000502:physiology; D018118:Chloride Channels / Q000502:physiology*; D002712:Chlorides / Q000378:metabolism; D007038:Hypotonic Solutions; D007700:Kinetics; D008114:Liver Neoplasms, Experimental / Q000473:pathology* / Q000503:physiopathology; D008954:Models, Biological; D051381:Rats; D018048:Receptors, Purinergic P2 / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction; D013498:Suramin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D018118:Chloride Channels; D002712:Chlorides; D007038:Hypotonic Solutions; D018048:Receptors, Purinergic P2; C022571:adenosine 5'-O-(3-thiotriphosphate); D013498:Suramin; D000255:Adenosine Triphosphate; D001081:Apyrase