In neurons of dorsal motor nucleus of the vagus that is involved in the gastric motility and possibly
emesis, application of
5-hydroxytryptamine produces membrane depolarization, and suppresses spike-repolarization and spike-afterhyperpolarization, suggesting divergent effects of
5-hydroxytryptamine through activating multiple subtypes of
5-hydroxytryptamine receptors. However, only the role of
5-hydroxytryptamine 2A receptors has been established to be responsible for the depolarization, and the mechanisms underlying the modulation of spikes remain unknown although a role of
5-hydroxytryptamine 4 receptors was implicated in modulations of spikes. There is now increasing evidence for the role of
5-hydroxytryptamine receptors in neurons involved in generating
emesis following administration of anticancer
drug. Since antagonists of
5-hydroxytryptamine 3/4 receptors are widely used as
anti-emetic drugs, we have reevaluated the functional roles of
5-hydroxytryptamine 3/4 receptors of dorsal motor nucleus of the vagus neurons, especially in modulating transient outward currents that are presumed to be involved in spike-repolarization and spike-afterhyperpolarization. Whole-cell patch-clamp recordings were made from the dorsal motor nucleus of the vagus neurons, which were identified by a retrograde tracing method with
dextran-tetramethylrhodamine-
lysine injected into a bundle of abdominal vagus nerves. Under a voltage-clamp condition, dorsal motor nucleus of the vagus neurons expressed a prominent A-like current. The activation of
5-hydroxytryptamine 3 receptors reversibly increased the resting membrane conductance while the activation of
5-hydroxytryptamine 4 receptors led to an almost irreversible decrease in the A-like current. A long-lasting suppression of A-like current by transient activation of
5-hydroxytryptamine 4 receptors would result in a long-lasting increase in the excitability of dorsal motor nucleus of the vagus neurons, which might be involved in generation of the long-lasting facilitation of gastric motility or in generation of the long-lasting gastric relaxation through the activation of enteric non-
adrenergic non-cholinergic neurons as implicated in the delayed
emesis induced by anticancer drugs.