5‐Hydroxytryptamine receptors of visceral primary afferent neurones on rabbit nodose ganglia

Abstract

1. The electrophysiological characteristics of 5-hydroxytryptamine (5-HT) receptors distributed on visceral primary afferent neurones (the nodose ganglion cells of the vagus) in rabbits were investigated with intracellular recording and voltage-clamp techniques.2. In response to 5-HT applied by superfusion (>/= 10 mum) or by ionophoresis (>/= 5 nA, 50 msec), the majority of type C neurones (mean axonal conduction velocity: 0.83+/-0.25 m/sec) showed a rapid depolarization of 20-30 mV in amplitude which was followed by a hyperpolarization of a few millivolts. Both the initial depolarization and afterhyperpolarization were associated with a reduction in membrane resistance.3. Type A neurones (mean axonal conduction velocity: 7.7+/-0.4 m/sec) did not show any significant alterations in membrane potential and resistance during or after application of 5-HT.4. The initial depolarization induced by 5-HT was abolished by Na(+)-free Krebs solution and showed a reduction of a few millivolts in K(+)-free or Ca(2+)-free Krebs solution. The response in normal Krebs solution was reversed at a membrane potential level of +7.3+/-1.1 mV.5. The afterhyperpolarization disappeared in Na(+)-free or Ca(2+)-free Krebs solution, while it was markedly enhanced in K(+)-free Krebs solution. The response in normal Krebs solution reversed at a membrane potential of -88.7+/-0.8 mV, and was abolished at membrane potentials more positive than -20 mV.6. Unlike 5-HT voltage responses, which were biphasic in the majority of neurones examined, 5-HT induced currents were usually monophasic when recorded at holding membrane levels ranging from -80 to +50 mV. The reversal potential of the inward current was +7.5+/-0.8 mV which was in good agreement with the reversal level for 5-HT-induced depolarizations. The reversal potentials for inward currents which were obtained at various concentrations of Na(+) or K(+) corresponded to the theoretical values calculated by the equivalent circuit equation.7. These results suggest that the initial depolarization induced by 5-HT is due mainly to simultaneous increases in Na(+) and K(+) conductances, while the afterhyperpolarization is brought about by an increase of K(+) conductance which is triggered by a voltage-dependent influx of Na(+) and Ca(2+).8. The mean value for the ;limiting slope' of conductance change vs. 5-HT concentration and the slope of 5-HT current vs. 5-HT concentration obtained by superfusion of 5-HT, were in good agreement, 1.84+/-0.26 and 1.88+/-0.31, respectively. On the other hand, the mean Hill coefficient obtained from the dose-response curves for the inward current induced by ionophoresis was 2.51+/-0.14.9. Tetrodotoxin (0.2 mum) blocked the soma action potential completely, but did not show any effect on 5-HT-induced responses.10. (+)-Lysergic acid diethylamide and methysergide (1-100 mum) had no depressant effect on the 5-HT-induced depolarization.11. (+)-Tubocurarine at low concentrations (1-5 mum) inhibited the 5-HT induced inward current competitively. The mode of its inhibitory action became noncompetitive at higher concentrations (10-20 mum).