Tonic GABAA Receptor-Mediated Inhibition in the Rat Dorsal Motor Nucleus of the Vagus

Type A gamma-aminobutyric acid (GABA(A)) receptors expressed in the dorsal motor nucleus of vagus (DMV) critically regulate the activity of vagal motor neurons and, by inference, the gastrointestinal (GI) tract. Two types of GABA(A) receptor-mediated inhibition have been identified in the brain, represented by phasic (I(phasic)) and tonic (I(tonic)) inhibitory currents. The hypothesis that I(tonic) regulates neuron activity was tested in the DMV using whole cell patch-clamp recordings in transverse brain stem slices from rats. An I(tonic) was present in a subset of DMV neurons, which was determined to be mediated by different receptors than those mediating fast, synaptic currents. Preapplication of tetrodotoxin significantly decreased the resting I(tonic) amplitude in DMV neurons, suggesting that most of the current was due to action potential (AP)-dependent GABA release. Blocking GABA transport enhanced I(tonic) and multiple GABA transporters cooperated to regulate I(tonic). The I(tonic) was composed of both a gabazine-insensitive component that was nearly saturated under basal conditions and a gabazine-sensitive component that was activated when extracellular GABA concentration was elevated. Perfusion of THIP (10 muM) significantly increased I(tonic) amplitude without increasing I(phasic) amplitude. The I(tonic) played a major role in determining the overall excitability of DMV neurons by contributing to resting membrane potential and AP frequency. Our results indicate that I(tonic) contributes to DMV neuron membrane potential and activity and is thus an important regulator of vagally mediated GI function.