FACILITATION OF MINIATURE GABAERGIC CURRENTS BY RUTHENIUM RED IN NEONATAL RAT HIPPOCAMPAL-NEURONS

The whole cell configuration of the patch-clamp technique was used to study the modulation gamma-aminobutyric acid (GABA)-mediated postsynap tic currents by ruthenium red in CA3 hippocampal neurons in slices obt ained from postnatal (P) days P6-P10 old rats. In the presence of kynu renic acid (1 mM), ruthenium red (100 mu M) completely blocked stimulu s-elicited GABA-mediated postsynaptic currents and reduced by 50% the amplitude of the spontaneous ones. Ruthenium red (100 mu M) increased the frequency but not the amplitude of miniature GABAergic currents re corded in the presence of tetrodotoxin (1 mu M) and kynurenic acid (1 mM), an effect that was prevented by heparin (100 mu M). Ruthenium red did not modify the kinetics of miniature postsynaptic currents and th e currents induced by exogenous application of GABA (10 mu M) in the p resence of tetrodotoxin, suggesting that its action was presynaptic in origin. The effects of ruthenium red on quantal GABA release was inde pendent of external calcium. In a nominally Ca2+-free solution the pot entiating effect induced by this polyvalent cation on miniature postsy naptic currents was still present. Intracellular calcium stores were n ot involved in ruthenium red action, because this polyvalent cation wa s able to facilitate miniature currents also in the presence of thapsi gargin (10-20 mu M). These results indicate that ruthenium red has a d ual action on GABA release from GABAergic interneurons: it reduces the amplitude of spontaneous events and increases the frequency of miniat ure currents. The former effect is calcium-dependent, whereas the latt er is calcium independent.