Protein kinase Cε is involved in ethanol potentiation of glycine-gated Cl- current in rat neurons of ventral tegmental area

Previously, we demonstrated that ethanol potentiates glycine current (I-Gly) in 35% of neurons freshly isolated from the ventral tegmental area (VTA) of rats (J. Pharmacol. Exp. Ther. 296 (2001) 77). In the present study, we examined the role of protein kinase C (PKC) in this action of ethanol on VTA neurons from young rats. Extracellular ethanol and intracellular ATP-gamma-S when applied separately potentiated I-Gly. However, ethanol potentiation of I-Gly was significantly reduced in neurons dialyzed with 2 mM ATP-gamma-S. Phorbol-12-myristate-13-acetate (PMA, 10 nM), a PKC activator also increased I-Gly and reduced ethanol potentiation of I-Gly. In addition, GF109203X (0.2 muM), a PKC inhibitor antagonized the potentiation effects produced either by PMA or by ethanol. Thus, ethanol potentiation of I-Gly may be associated with PKC activation. While intracellular application of 1,2-bis(aminophenoxy)ethane-N,N,N,N'-tetraacetic acid, a Ca2+ chelator or Go6976, an inhibitor of Ca2+-dependent PKC had no appreciable effect on ethanol potentiation of I-Gly, translocation inhibitor peptide (PKCepsilon-TIP) (500 nM) significantly reduced ethanol potentiation, an action the translocation inhibitor peptide negative control (PKCepsilon-TIP-NC) (500 nM) did not have. These results suggest that the activation of PKCepsilon isoenzyme contributes to ethanol-induced potentiation of GlyR function. (C) 2003 Elsevier Science Ltd. All rights reserved.