Protein kinase C epsilon 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 microM), 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 Ca(2+) chelator or Gö6976, an inhibitor of Ca(2+)-dependent PKC had no appreciable effect on ethanol potentiation of I(Gly), translocation inhibitor peptide (PKC(epsilon)-TIP) (500 nM) significantly reduced ethanol potentiation, an action the translocation inhibitor peptide negative control (PKC(epsilon)-TIP-NC) (500 nM) did not have. These results suggest that the activation of PKC(epsilon) isoenzyme contributes to ethanol-induced potentiation of GlyR function.
Jiang
Z L
ZL
Department of Anesthesiology, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103-2714, USA.
Ye
J-H
JH
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002614:Chelating Agents / Q000494:pharmacology; D018118:Chloride Channels / Q000502:physiology*; D000431:Ethanol / Q000494:pharmacology*; D005998:Glycine / Q000502:physiology*; D066298:In Vitro Techniques; D015640:Ion Channel Gating; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D051744:Protein Kinase C-epsilon; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D017557:Ventral Tegmental Area / Q000166:cytology / Q000187:drug effects* / Q000502:physiology
D002614:Chelating Agents; D018118:Chloride Channels; C022571:adenosine 5'-O-(3-thiotriphosphate); D000431:Ethanol; D000255:Adenosine Triphosphate; C497257:Prkce protein, rat; D011493:Protein Kinase C; D051744:Protein Kinase C-epsilon; D002118:Calcium; D005998:Glycine