title: Enhancement of tonic and phasic GABAergic currents following nitric oxide synthase inhibition in hippocampal CA1 pyramidal neurons.
abstract: Nitric oxide (NO) is involved in synaptic plasticity in the hippocampus through different presynaptic and postsynaptic mechanisms that include the modulation of the GABAergic neurotransmission. Inhibitory synapses on hippocampal pyramidal neurons are known to possess the molecular machinery for retrograde NO-signaling, but the modulation of GABAARs function by NO in these neurons and the mechanisms of action involved have not been fully characterized. Here we show that suppression of the endogenous NO generation by the nitric oxide synthase (NOS) inhibitor L-NAME produces significant and reversible increases in the magnitude of both tonic and phasic GABAergic currents in CA1 hippocampal pyramidal neurons. GABA-evoked chloride currents were measured in the presence or absence of L-NAME using whole-cell patch-clamp recordings in acute hippocampal slices from young adult mice. Enhancement of the tonic GABA responses induced by L-NAME was insensitive to TTX and decreased by co-incubation with the NO donor DEA/NO. Applications of DEA/NO alone did not produce significant effects on tonic GABA responses. L-NAME treatment also increased the amplitude of phasic GABAergic currents evoked by GABA-puffs. Our results indicate that the extent of tonic and phasic inhibition mediated by GABAA receptors in CA1 hippocampal pyramidal neurons is affected by endogenous NO production.
authors: Laboratorio de Neurobiología Celular y Molecular Instituto de Investigaciones en Ingeniería Genética y Biología Molecular (INGEBI) "Dr. Héctor N. Torres", Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Vuelta de Obligado 2490, Ciudad Autónoma de Buenos Aires (CP 1428), Argentina.
authors: Javier
authors: J
authors: Gasulla
authors: Laboratorio de Neurobiología Celular y Molecular Instituto de Investigaciones en Ingeniería Genética y Biología Molecular (INGEBI) "Dr. Héctor N. Torres", Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Vuelta de Obligado 2490, Ciudad Autónoma de Buenos Aires (CP 1428), Argentina. Electronic address: danieljcalvo@gmail.com.
authors: Daniel J
authors: DJ
authors: Calvo
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D008807:Mice, Inbred BALB C; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D017966:Pyramidal Cells / Q000187:drug effects* / Q000502:physiology; D011963:Receptors, GABA-A / Q000502:physiology; D009435:Synaptic Transmission; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
chemical_list: D011963:Receptors, GABA-A; D009569:Nitric Oxide; D005680:gamma-Aminobutyric Acid; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester
keywords: GABA(A) receptors; Hippocampus; Nitric oxide synthase; Phasic inhibition; Tonic inhibition