PMID- 8138953
OWN - NLM
STAT- MEDLINE
DCOM- 19940425
LR  - 20131121
IS  - 0022-3565 (Print)
IS  - 0022-3565 (Linking)
VI  - 268
IP  - 3
DP  - 1994 Mar
TI  - Potentiation of GABAA-mediated synaptic current by ethanol in hippocampal CA1 
      neurons: possible role of protein kinase C.
PG  - 1388-95
AB  - Ethanol has been reported to interact with numerous voltage- and ligand-gated ion 
      channels in central mammalian neurons. In particular, the type A 
      gamma-aminobutyric acid (GABAA) receptor/chloride ionophore complex has received 
      considerable attention as a cellular substrate for ethanol and other 
      sedative-hypnotic drugs. Direct electrophysiological evidence that ethanol 
      modulates GABAA receptor function has been controversial. In this study, we 
      investigated the effects of ethanol on the GABAA receptors that mediate fast 
      inhibitory synaptic transmission in the rat hippocampus. Using the whole-cell 
      patch-clamp recording technique in brain slices, we found that clinically 
      relevant concentrations of ethanol (10-50 mM) potentiate pharmacologically 
      isolated GABAA-mediated inhibitory postsynaptic currents (IPSCs) recorded from 
      rat hippocampal CA1 neurons. In addition, we demonstrate that ethanol- but not 
      diazepam-mediated enhancement of GABAA IPSCs requires intracellular ATP and can 
      be blocked by Ro-31-8220 or PKC19-31, specific inhibitors of protein kinase C. 
      Furthermore, the active phorbol ester 4-beta-PDBu but not its inactive analog 
      also interferes with ethanol enhancement of GABAA IPSCs. These results 
      demonstrate that ethanol potentiation of pharmacologically isolated GABAA IPSCs 
      can be modulated by protein kinase C.
FAU - Weiner, J L
AU  - Weiner JL
AD  - Playfair Neuroscience Unit, Toronto Hospital Research Institute, Ontario, Canada.
FAU - Zhang, L
AU  - Zhang L
FAU - Carlen, P L
AU  - Carlen PL
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Pharmacol Exp Ther
JT  - The Journal of pharmacology and experimental therapeutics
JID - 0376362
RN  - 0 (Receptors, GABA)
RN  - 37558-16-0 (Phorbol 12,13-Dibutyrate)
RN  - 3K9958V90M (Ethanol)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - EC 2.7.11.13 (Protein Kinase C)
SB  - IM
MH  - Adenosine Triphosphate/metabolism
MH  - Animals
MH  - Ethanol/antagonists & inhibitors/*pharmacology
MH  - Hippocampus/cytology/*drug effects/metabolism
MH  - Male
MH  - Neurons/*drug effects/metabolism/physiology
MH  - Phorbol 12,13-Dibutyrate/pharmacology
MH  - Protein Kinase C/antagonists & inhibitors/*metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Receptors, GABA/*drug effects/metabolism
MH  - Synapses/*drug effects/physiology
EDAT- 1994/03/01 00:00
MHDA- 1994/03/01 00:01
CRDT- 1994/03/01 00:00
PHST- 1994/03/01 00:00 [pubmed]
PHST- 1994/03/01 00:01 [medline]
PHST- 1994/03/01 00:00 [entrez]
PST - ppublish
SO  - J Pharmacol Exp Ther. 1994 Mar;268(3):1388-95.