PROPERTIES OF GABA(A) RECEPTORS IN CULTURED RAT OLIGODENDROCYTE PROGENITOR CELLS

We have studied the properties of GABA responses in oligodendrocyte-ty pe 2 astrocyte (O-2A) progenitor cells derived from primary cultures o f the neonatal rat brain. In whole cell voltage clamp recordings, rapi d application of 1-10 mM GABA elicited current responses in > 85% of t he cells examined. The dose-response relationship pooled from nine pro genitor cells was best fit by a logistic function of EC50 = 113 mu M a nd Hill coefficient = 0.9. In contrast to the rate of current deactiva tion, the rate of current activation exhibited marked concentration-de pendence. Pharmacologically, GABA, muscimol and ZAPA ((Z)3[(aminiimino methyl)thio]prop-2-enoic acid sulphate) produced responses with ligand -specific kinetics, whereas glycine and the GABA(C) receptor agonist C ACA were without effect; bicuculline methochloride acted as a competit ive antagonist. Neither the amplitude nor the kinetics of currents pro duced by 100 mu M GABA were affected by the benzodiazepine flunitrazep am (1 mu M). Similarly the benzodiazepine receptor inverse agonist DMC M (1 mu M) was also without effect. GABA-activated currents reversed p olarity within 2 mV of the calculated Cl- equilibrium potential. With brief agonist pulses deactivation was monoexponential, however, unlike neurones the rate of deactivation was voltage-independent. Desensitis ation of responses to 10 mM GABA was bi-exponential and accelerated at depolarised membrane potentials. Increasing the amount of GABA(A) rec eptor desensitisation (by increasing the duration of the agonist expos ure) consistently produced a slowing of deactivation. (C) 1998 Elsevie r Science Ltd. All rights reserved.