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 postsynaptic currents by ruthenium red in CA3 hippocampal neurons in slices obtained from postnatal (P) days P6-P10 old rats. In the presence of kynurenic acid (1 mM), ruthenium red (100 microM) completely blocked stimulus-elicited GABA-mediated postsynaptic currents and reduced by 50% the amplitude of the spontaneous ones. Ruthenium red (100 microM) increased the frequency but not the amplitude of miniature GABAergic currents recorded in the presence of tetrodotoxin (1 microM) and kynurenic acid (1 mM), an effect that was prevented by heparin (100 microM). Ruthenium red did not modify the kinetics of miniature postsynaptic currents and the currents induced by exogenous application of GABA (10 microM) in the presence of tetrodotoxin, suggesting that its action was presynaptic in origin. The effects of ruthenium red on quantal GABA release was independent of external calcium. In a nominally Ca2+-free solution the potentiating effect induced by this polyvalent cation on miniature postsynaptic currents was still present. Intracellular calcium stores were not involved in ruthenium red action, because this polyvalent cation was able to facilitate miniature currents also in the presence of thapsigargin (10-20 microM). These results indicate that ruthenium red has a dual action on GABA release from GABAergic interneurons: it reduces the amplitude of spontaneous events and increases the frequency of miniature currents. The former effect is calcium-dependent, whereas the latter is calcium independent.
Sciancalepore
M
M
Neuroscience Programme and Istituto Nazionale Fisica della Materia Unit, International School for Advanced Studies, 34014 Trieste, Italy.
Savić
N
N
Györi
J
J
Cherubini
E
E
D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism; D004336:Drug Antagonism; D006493:Heparin / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D066298:In Vitro Techniques; D009474:Neurons / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000502:physiology; D012430:Ruthenium Red / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism / Q000502:physiology*
D011963:Receptors, GABA-A; D012430:Ruthenium Red; D005680:gamma-Aminobutyric Acid; D006493:Heparin; D002118:Calcium