Ethanol suppresses fast potentiation of glycine currents by glutamate.
Excitatory (glutamate) and inhibitory (GABA(A) and glycine) receptor/channels coexist in many neurons. To assess effects of ethanol on the interaction of glutamate and glycine receptors, glycine-induced current (I(Gly)) 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 microM 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 EC(50) for glycine and increased the maximal I(Gly). 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 I(Gly) in 35% of neurons from the ventral tegmental area. In contrast, when coapplied with glutamate and glycine, ethanol suppressed the glutamate-induced potentiation of I(Gly) 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 I(Gly). These findings suggest that glutamate-induced calcium influx modulates glycine receptors by a mechanism that can be blocked by ethanol.
Department of Anesthesiology, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103-2714, USA.
Li
L
Zhu
Kresimir
K
Krnjević
Zhenghlin
Z
Jiang
Joseph J
JJ
McArdle
Jiang Hong
JH
Ye
D000818:Animals; D002118:Calcium / Q000502:physiology; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D004533:Egtazic Acid / Q000494:pharmacology; D004594:Electrophysiology; D000431:Ethanol / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D018698:Glutamic Acid / Q000494:pharmacology*; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000187:drug effects; D018009:Receptors, Glycine / Q000187:drug effects*; D017557:Ventral Tegmental Area / Q000187:drug effects
D002492:Central Nervous System Depressants; D018691:Excitatory Amino Acid Antagonists; D017470:Receptors, Glutamate; D018009:Receptors, Glycine; D000431:Ethanol; D018698:Glutamic Acid; D004533:Egtazic Acid; D002118:Calcium