Autocrine Signaling through ATP Release Represents a Novel Mechanism for Cell Volume Regulation
- Resource Type
- research-article
- Authors
- Wang, Yu; Roman, Richard; Lidofsky, Steven D.; Fitz, J. Gregory
- Source
- Proceedings of the National Academy of Sciences of the United States of America, 1996 Oct . 93(21), 12020-12025.
- Subject
- Physiology
Cl$^{-}$ channel
Patch clamp
Purinergic
Receptors
Hepatocytes
Swelling
Liver cells
Epithelial cells
Cell lines
Cell membranes
Physiological regulation
Cell physiology
Cell surface receptors
- Language
- English
- ISSN
- 00278424
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 (P$_{2}$) 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 $\pm $ 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 P$_{2}$ receptor blockers suramin and Reactive Blue 2 (10-100 $\mu $M). Cell swelling also stimulated release of ATP. Hypotonic exposure increased the concentration of ATP in the effluent of perfused cells by 170 $\pm $ 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 $\approx $30-fold to 16.5 $\pm $ 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 P$_{2}$ receptors.