Activation of both phasic and tonic GABAA¬ receptors modulates vagal efferent outflow regulating gastric motor functions

Abstract

The dorsal motor nucleus of the vagus (DMV) provides the parasympathetic innervation to the stomach. DMV neurons display both synaptic and extrasynaptic GABAA receptors that are activated by phasic and tonic GABA release, respectively. Studies have demonstrated that ongoing activation of GABAA receptors is critical in determining vagal efferent outflow to the stomach. The present study was designed to investigate whether phasic and/or tonic GABAA receptors are involved in the regulation of gastric tone.Miniaturized strain gauges were sutured to the ventral surface of the gastric corpus in male Sprague‐Dawley rats (175–300g). The GABAA receptor antagonists, gabazine (0.78–6.25pmol) and/or bicuculline methiodide (BMI; 25–100pmol), were microinjected into the dorsal vagal complex and the increase in gastric tone expressed relative to the maximal increase induced following i.v. application of the non‐selective muscarinic agonist, bethanecol (352pmol; 1ml). At low doses, gabazine acts selectively on extrasynaptic receptors, whereas BMI acts on both synaptic and extrasynaptic receptors.Gabazine increased gastric tone 5.1±1.7% at 0.78pmol, n=10, increasing to 15.3±1.74% and 19.1±5.94% in response to 3.125 and 6.25pmol, n = 5,6, respectively (P<0.05 vs 0.78pmol for each). At lower doses, BMI induced similar increases in gastric tone (11.0±4.7% and 14.9±5.5% at 25 and 50pmol, n = 8,8, respectively) whereas the response was significantly greater at 100pmol (35.7±17.8%, n=4, P<0.05). These data suggest that the activity of DMV neurons, hence vagal efferent outflow to the stomach, is regulated by both synaptic and extrasynaptic GABAA receptors implying a more complex synaptic modulation than previously considered.Supported by NSF IOS 11489364