ALLOSTERIC MODULATION OF GABA(A) RECEPTORS IN ACUTELY DISSOCIATED NEURONS OF THE SUPRACHIASMATIC NUCLEUS

The gamma-aminobutyric acid (GABA)-induced response was investigated i n acutely dissociated suprachiasmatic nucleus (SCN) neurons of 11- to 14-day-old rats, under the voltage-clamp condition of nystatin-perfora ted patch recording. At a holding potential of -40 mV, application of GABA induced inward currents in a concentration-dependent manner. Pent obarbital and 5 beta-pregnan-3 alpha-ol-20-one (pregnanolone) similarl y induced inward currents, GABA-induced inward currents were suppresse d in a concentration-dependent manner by pretreating neurons with a GA BA(A) receptor antagonist, bicuculline. Bicuculline (3 x 10(-6) M) shi fted the concentration-response curve of GABA to the left in a competi tive manner. Reversal potential of the GABA response (E(GABA)) was -3. 4 +/- 0.7 mV, close to the theoretical Cl- equilibrium potential of -4 .1 mV. Pretreating SCN neurons with diazepam, pentobarbital, and pregn anolone enhanced the 3 x 10(-6) NI GABA response. Diazepam (3 x 10(-8) M), pentobarbital (3 x 10(-5) M), and pregnanolone (10(-7) M) shifted the concentration-response curve of GABA to the left without changing the maximal amplitude of GABA responses. E(GABA) in the presence of d iazepam, pentobarbital, or pregnanolone was the same as that in their absence. These results show that the GABA response in acutely dissocia ted SCN neurons is mediated by the GABA(A) receptor. Because the GABA( A) receptor of SCN neurons is allosterically augmented by diazepam, pe ntobarbital, and pregnanolone, similarly as in other regions of the ce ntral nervous system, the present study opens up ways to functionally modulate the GABA(A) receptors in SCN.