Ethanol enhances synaptically evoked GABAA receptor-mediated responses in cerebral cortical neurons in rat brain slices.
Previous intracellular electrophysiological studies on rat hippocampal brain slices have shown very little effect of acute ethanol application on synaptically evoked GABAA receptor-mediated responses recorded in CA1 pyramidal neurons. The present study was designed to compare the effects of ethanol on pyramidal neurons in the hippocampus and cerebral cortex. Using conventional intracellular microelectrodes (60-80 M omega) to impale cortical neurons in brain slices, 80 mM ethanol application did not affect the membrane input impedance nor evoked EPSPs, but significantly affected the resting membrane potential (usually a 2-5 mV hyperpolarization). When stimulus-evoked GABAA-mediated IPSCs were studied using whole-cell recordings from cortical neurons voltage-clamped at depolarizing potentials, monophasic IPSCs were evoked that were blocked by bicuculline, increased by pentobarbital, and enhanced by ethanol superfusion in a dose dependent manner over the range of 20-160 mM. Hippocampal IPSCs recorded under identical conditions were not enhanced by ethanol. Parallel studies of GABA-stimulated 36Cl- flux measurements in microsacs prepared from hippocampal, cerebral cortical and cerebellar tissue demonstrated that ethanol significantly enhanced (30-50%) 36Cl- flux in microsacs derived from the cerebral cortex and cerebellum, but not in microsacs prepared from the hippocampus. These results demonstrate that there are clear brain region-dependent differences in the way that GABAA receptor function is altered by acute ethanol, and that these differences are apparent not only as an enhancement of responses to exogenous GABA, but also as a facilitation of the responses to endogenous GABA released from inhibitory nerve terminals during synaptic activation.
Proctor
W R
WR
Department of Pharmacology, University of Colorado Health Sciences Center, Denver 80262.
Soldo
B L
BL
Allan
A M
AM
Dunwiddie
T V
TV
D000818:Animals; D002540:Cerebral Cortex / Q000166:cytology* / Q000187:drug effects; D002712:Chlorides / Q000378:metabolism; D004594:Electrophysiology; D000431:Ethanol / Q000494:pharmacology*; D005073:Evoked Potentials, Somatosensory / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009411:Nerve Endings / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects*; D013569:Synapses / Q000187:drug effects*
D002712:Chlorides; D011963:Receptors, GABA-A; D000431:Ethanol