Inhibition by ethanol of rat P2X(4) receptors expressed in Xenopus oocytes

1 The effect of ethanol on the function of P2X(4) receptors expressed in Xe nopus oocytes was studied using two-electrode voltage-clamp recording. 2 The amplitude of current activated by 1 mu M ATP was decreased by ethanol in a concentration-dependent manner over the concentration range 1-500 mM. The concentration of ethanol that produced 50% inhibition (IC50) of curren t activated by 1 mu M ATP was 58 mM. 3 Ethanol inhibition of ATP-activated current was not dependent on membrane potential from - 60 to + 20 mV, and ethanol did not change the reversal po tential of ATP-activated current. 4 Ethanol, 50 mM, shifted the ATP concentration-response curve to the right , increasing the EC50 for ATP from 9.1 to 16.0 mu M, but did not reduce the maximal response to ATP. 5 The results suggest that ethanol may inhibit P2X(4) receptors by decreasi ng the apparent affinity of the binding site for ATP. 6 Since the P2X(4) receptor is the most abundant P2X subunit in the brain, these receptors could be important effecters of ethanol action in the centr al nervous system.