RT Journal Article
SR Electronic
T1 Ethanol Suppresses Fast Potentiation of Glycine Currents by Glutamate
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 1193
OP 1200
DO 10.1124/jpet.102.033894
VO 302
IS 3
A1 Li Zhu
A1 Kresimir Krnjević
A1 Zhenghlin Jiang
A1 Joseph J. McArdle
A1 Jiang Hong Ye
YR 2002
UL http://jpet.aspetjournals.org/content/302/3/1193.abstract
AB Excitatory (glutamate) and inhibitory (GABAAand glycine) receptor/channels coexist in many neurons. To assess effects of ethanol on the interaction of glutamate and glycine receptors, glycine-induced current (IGly) was recorded by a whole-cell patch-clamp technique from neurons freshly dissociated from the ventral tegmental area of rats. A conditioning prepulse of glutamate (1–3 s, 1 mM) significantly and reversibly potentiated responses to a pulse of glycine. This potentiation was increased when extracellular calcium was raised to 12 mM and reduced by including 10 mM 1,2-bis-(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid in the internal recording medium. It was not affected by 5 μM 1-N,O-bis-(5-isoquinolinesulfonyl)-N-methyl-l-tyrosyl]-4-phenylpiperazine (KN-62), a selective inhibitor of calcium/calmodulin-dependent protein kinase II. In a concentration-response analysis, a conditioning pulse of glutamate significantly lowered the EC50 for glycine and increased the maximal IGly. Kinetic analysis of the currents indicated that glutamate slowed deactivation of glycine-gated chloride channels; therefore, glutamate may increase the affinity of glycine receptors for glycine. When coapplied with glycine, ethanol (10 mM) potentiated IGly in 35% of neurons from the ventral tegmental area. In contrast, when coapplied with glutamate and glycine, ethanol suppressed the glutamate-induced potentiation of IGly in these neurons. This suppression was also observed when ethanol and glycine were coapplied after a glutamate prepulse. A similar effect was observed when ethanol alone did not potentiate IGly. These findings suggest that glutamate-induced calcium influx modulates glycine receptors by a mechanism that can be blocked by ethanol. The American Society for Pharmacology and Experimental Therapeutics