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

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 μM, 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 (R(m), 22.7 ± 2.2%). These depolarizations and increases in R(m) (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 (E(rev)) of -91 ± 1 mV at an extracellular K⁺ concentration ([K⁺]₀) of 4.2 mM. This correlated well with the K⁺ equilibrium potential (E(K) = -89 mV). 3. The depolarizing effect of 5-HT was attenuated by the 5-HT(2A/2C) receptor antagonists, ketanserin (1 μM), LY 53,857 (1 μM) and the 5-HT(1A/2A) receptor antagonist, spiperone (1 μM). The 5-HT(1A) receptor antagonist, pindobind 5-HT(1A) (5 μM), had no effect on the depolarizing response to 5-HT. 4. The effect of 5-HT was mimicked by the 5-HT(2A/2C) receptor agonist, α-methyl-5-HT (50 μM), the 5-HT₃ receptor agonist, 5-carboxamidotryptamine (20 μM) and the putative 5-HT₄ agonist, 5-methyoxytryptamine (50 μM). 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 μM) and ICS-205-930 (1 and 10 μM), partially reduced the effect of 5-HT. The 5-HT₃ receptor agonist, 2-methyl-5-HT (100-300 μM), 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-HT(2A) receptors, being mediated, in part, by the reduction of K⁺ conductance.