Mechanism by which GABA, through its GABA(A) receptor, modulates glutamaterelease from rat cortical neurons in culture

In cortical neurons, the GABA(A) agonist, muscimol, increases: (a) basal gl utamate release (with a EC50 of 99+/-7 mu M); (b) intracellular calcium and (c) membrane potential, all of these in a dose-dependent manner. These mus cimol effects were specific since they were reversed by bicuculline, a GABA (A) antagonist. When the action of muscimol was measured at different KCI concentrations, a n increase or decrease of the glutamate secretion was observed, depending o n the KCl concentration in the medium. At low KCI concentration (5.6 mM of KCl), it depolarized, at 20 mM of KCl it had no effect, but at higher KCl c oncentrations (30-100 mu M of KCl), it produced a hyperpolarization in thes e cells. The mechanism by which the GABA-Cl--channel permits Cl- Buses. inward or ou tward, depending on the membrane potential. (C) 1999 Elsevier Science Ltd. All rights reserved.