GABA INDUCES GABAERGIC MSCS IN CULTURED EMBRYONIC RAT THALAMIC NEURONS

Application of 0.1-10 mu M GABA in the vicinity of cultured embryonic rat thalamic neurons recorded with patch pipettes in the presence of 2 mu M TTX induced or increased the frequency of miniature synaptic cur rents (MSCs) that reversed polarity at the Cl- equilibrium potential. These MSCs were blocked by the GABA(A) receptor antagonist bicuculline and exhibited exponential decay kinetics that closely paralleled thos e estimated from fluctuation analysis of Cl- channels activated pharma cologically by applying 1-10 mu M GABA to the same cells. We conclude that the MSCs are mediated by GABA. Application of the GABA(A) recepto r agonist muscimol activated Cl- current but failed to induce GABAergi c MSCs while submicromolar concentrations of GABA evoked GABAergic MSC s but did not activate Cl- channels. The GABA(B) receptor agonist (-)b aclofen did not mimic GABA in inducing MSCs. Induction of GABAergic MS Cs by GABA required extracellular Ca2+. Verapamil and Co2+, which bloc k voltage-dependent calcium channels, completely blocked GABA-induced MSCs independent of their effects on the direct activation of a Cl- cu rrent response. The results indicate that GABA can trigger GABAergic C l--dependent MSCs in a Ca-o(2+)-dependent manner. The mechanism may in volve a novel receptor and/or signal transduction pathway. (C) 1997 Wi ley-Liss, Inc.