ETHANOL SELECTIVELY ENHANCES THE HYPERPOLARIZING COMPONENT OF NEOCORTICAL NEURONAL RESPONSES TO LOCALLY APPLIED GABA

Local application of GABA to rat cerebral cortical neurons in brain sl ices elicited biphasic responses mediated via GABA(A) receptors. The f ast component of the response, which was most apparent with somatic ap plication of GABA, was hyperpolarizing at the normal resting membrane potential (GABA(h) response). The slower component could be elicited b y GABA application to nearly all regions of the cell, and was depolari zing at the resting membrane potential (GABA(d) response). The reversa l potential of evoked IPSCs recorded with whole-cell patch electrodes (- 68 mV) was comparable to the reversal potential of the GABA(h) resp onse (- 69 mV), and was significantly different from the reversal pote ntial of the GABA(d) response (- 56 mV). The GABA(d) response was more sensitive to enhancement by pentobarbital and more readily antagonize d by both bicuculline and picrotoxin than the GABA(h) response. Record ing in bicarbonate-free buffer changed the reversal potential of the G ABA(d) response significantly, but had no effect on the GABA(h) respon se. In contrast, superfusion with ethanol significantly enhanced the G ABA(h) response, while having no effect on the GABA(d) component. Alth ough a localized collapse of the Cl- gradient, which has been proposed to underlie the GABA(d) response, could explain the greater sensitivi ty of the GABA(d) response to pentobarbital and the GABA(A) antagonist s, this could not account for the greater sensitivity of the GABA(h) r esponse to ethanol. Differences in GABA(A) receptor subunit compositio n may result in the expression of dendritic and somatic GABA(A) recept ors that have different kinetics, reversal potentials, and sensitivity to pharmacological agents, including ethanol. (C) 1998 Elsevier Scien ce B.V. All rights reserved.