Ethanol suppresses fast potentiation of glycine currents by glutamate

Li Zhu, Kresimir Krnjevi, Zhenghlin Jiang, Joseph J. McArdle, Jiang Hong Ye

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Excitatory (glutamate) and inhibitory (GABAA and 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 glycinegated 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.

Original languageEnglish (US)
Pages (from-to)1193-1200
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume302
Issue number3
DOIs
StatePublished - Sep 2002

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

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