The effect of 5-HT and selective 5-HT receptor agonists and antagonists on rat dorsal vagal preganglionic neurones in vitro

Abstract

1. Whole-cell patch-clamp recordings were made from 142 visually identified rat dorsal vagal preganglionic neurones (DVMs). Applications of 5-hydroxytryptamine (5-HT, 20 microM, 2 min) elicited a slow depolarization (8.2 +/- 0.5 mV, n = 59) in 95% of the cells tested, accompanied by an increase in excitability. In (68%) of DVMs the depolarization was associated with an increase in apparent membrane resistance (Rmt 22.7 +/- 2.2%). These depolarizations and increases in Rm (14.3 +/- 2.6%, n = 8) were maintained in a medium which blocked synaptic transmission. 2. The response to 5-HT was associated with a reversal potential (Erev) of -91 +/- 1 mV at an extracellular K+ concentration (LK+]o) of 4.2 mM. This correlated well with the K+ equilibrium potential (Ek = -89 mV). 3. The depolarizing effect of 5-HT was attenuated by the 5-HT2A/2C receptor antagonists, ketanserin (1 microM), LY 53,857 (1 microM) and the 5-HT1A/2A receptor antagonist, spiperone (1 microM). The 5-HT1A receptor antagonist, pindobind 5-HT1A (5 microM), had no effect on the depolarizing response to 5-HT. 4. The effect of 5-HT was mimicked by the 5-HT2A/2C receptor agonist, alpha-methyl-5-HT (50 microM), the 5-HT1 receptor agonist, 5-carboxamidotryptamine (20 microM) and the putative 5-HT4 agonist, 5-methyoxytryptamine (5 microM). The selective 5-HT4 receptor antagonist, GR113808, had no effect on the depolarizing effect of 5-HT or 5-MEOT on DVMs. 5. The 5-HT3 antagonists, MDL 72222 (10 microM) and ICS-205-930 (1 and 10 microM), partially reduced the effect of 5-HT. The 5-HT3 receptor agonist, 2-methyl-5-HT (100-300 microM), excited a proportion of neurones tested (56%) by evoking a depolarizing and/or an increase in postsynaptic potentials (p.s.ps). 6. These results are consistent with direct, postsynaptic actions of 5-HT on DVMs via 5-HT2A receptors, being mediated, in part, by the reduction of K+ conductance.