Abstract
In order to explore the facilitatory GABAergic control of central noradrenergic neurons, we investigated the effect of muscimol, a GABAA receptor agonist, on spontaneous excitatory postsynaptic currents in mechanically dissociated rat locus coeruleus neurons attached with native glutamtatergic nerve terminals. The activation of presynaptic GABAA receptors by muscimol facililtates spontaneous glutamate release by activating tetrodotoxin-sensitive Na+ channels and high-threshold Ca2+ channels. This depolarizng action of muscimol was caused by an outwardly directed Cl− driving force for GABAA receptors; that is, intracellular Cl− concentration of glutamatergic nerve terminals was higher than that predicted for a passive distribution. The higher Cl− concentration was generated by bumetanide-sensitive Na-K-Cl cotransporters and was responsible for the GABAA receptor-mediated presynaptic depolarization. Thus, GABAA receptor-mediated modulation of spontaneous glutamatergic transmission may contribute to the regulation of activity of locus coeruleus noradrenergic neurons. [Jpn J Physiol 54 Suppl:S149 (2004)]
