Inhibition of mechanosensitivity in visceral primary afferents by GABAB receptors involves calcium and potassium channels

GABAB receptors inhibit mechanosensitivity of visceral afferents. This is associated with reduced triggering of events that lead to gastro-esophageal reflux, with important therapeutic consequences. In other neuronal systems, GABAB receptor activation may be linked via G-proteins to reduced N-type Ca2+ channel opening, increased inward rectifier K+ channel opening, plus effects on a number of intracellular messengers. Here we aimed to determine the role of Ca2+ and K+ channels in the inhibition of vagal afferent mechanoreceptor function by the GABAB receptor agonist baclofen. The responses of three types of ferret gastro-esophageal vagal afferents (mucosal, tension and tension mucosal receptors) to graded mechanical stimuli were investigated in vitro. The effects of baclofen (200μM) alone on these responses were quantified, and the effects of baclofen in the presence of the G-protein-coupled inward rectifier potassium channel blocker Rb+ (4.7mM) and/or the N-type calcium channel blocker ω-conotoxin GVIA (0.1μM). Baclofen inhibition of mucosal receptor mechanosensitivity was abolished by both blockers. Its inhibitory effect on tension mucosal receptors was partly reduced by both. The inhibitory effect of baclofen on tension receptors was unaffected. The data indicate that the inhibitory action of GABAB receptors is mediated via different pathways in mucosal, tension and tension mucosal receptors via mechanisms involving both N-type Ca2+ channels and inwardly rectifying K+ channels and others.