Supported, in part, by PHS grants RO1 AA03972 from the NIAAA, NIH, and the Alcohol Beverage Medical Research Foundation.
Ethanol Sensitivity in ATP-Gated P2X Receptors Is Subunit Dependent
Article first published online: 11 APR 2006
Alcoholism: Clinical and Experimental Research
Volume 26, Issue 6, pages 773–778, June 2002
How to Cite
Davies, D. L., Machu, T. K., Guo, Y. and Alkana, R. L. (2002), Ethanol Sensitivity in ATP-Gated P2X Receptors Is Subunit Dependent. Alcoholism: Clinical and Experimental Research, 26: 773–778. doi: 10.1111/j.1530-0277.2002.tb02604.x
- Issue published online: 11 APR 2006
- Article first published online: 11 APR 2006
- Received for publication March 15, 2002; accepted March 21, 2002.
- P2X Receptors;
- Ligand-Gated Ion Channels;
- Adenosine 5′-Triphosphate;
- Xenopus Oocytes
Background: P2X receptors are ligand-gated cation channels that are gated by synaptically released extracellular adenosine 5′-triphosphate (ATP). P2X receptors are inhibited by ethanol; however, few investigations have focused on ethanol's effects in P2X receptors. Recently, recombinant homomeric P2X4 receptors were reported to be sensitive to ethanol's inhibitory action, whereas recombinant P2X3 receptors were insensitive to ethanol. The two recombinant studies were conducted in different expression systems by using different techniques; therefore, questions remain. The present study tests the hypothesis that ethanol sensitivity in P2X receptors is subunit dependent.
Methods: The effects of ethanol (25–200 mM ± ATP) on rat recombinant homomeric P2X2 and P2X4 receptors expressed in Xenopus oocytes were tested by using two-electrode voltage clamp techniques.
Results: Ethanol inhibited EC10 ATP-gated currents significantly less in P2X2 versus P2X4 receptors. A second study found that ethanol right-shifted the ATP concentration-response curve in P2X2 receptors, which significantly increased the EC50 for ATP without altering the Hill slope or maximal current response to ATP. These latter characteristics of ethanol action in P2X2 receptors agree with previous work in P2X4 receptors. There was no effect of ethanol when tested in the absence of ATP.
Conclusion: The findings are the first to show (1) ethanol inhibition of ATP-activated currents on P2X2 receptors, (2) differences in ethanol sensitivity between homomeric P2X receptors when tested under matched conditions, and (3) evidence that suggests similar mechanisms of ethanol action for P2X2 and P2X4 receptors. These findings provide the first direct support for the hypothesis that ethanol sensitivity in P2X receptors is subunit dependent.