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

Abstract

The electrophysiological characteristics of 5-hydroxytryptamine (5-HT) receptors distributed on visceral primary afferent neurons (the nodose ganglion cells of the vagus) in rabbits were investigated with intracellular recording and voltage-clamp techniques. In response to 5-HT applied by superfusion (.gtoreq. 10 .mu.M) or by iontophoresis (.gtoreq. 5 nA, 50 ms), the majority of type C neurons (mean axonal conduction velocity: 0.83 .+-. 0.25 m/s) showed a rapid depolarization of 20-30 mV in amplitude, followed by a hyperpolarization of a few millivolts. Both initial depolarization and afterhyperpolarization were associated with a reduction in membrane resistance. Type A neurons (mean axonal conduction velocity: 7.7 .+-. 0.4 m/s) did not show any significant alterations in membrane potential and resistance during or after application of 5-HT. 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 Ca2+-free Krebs solution. The response in normal Krebs solution was reversed at a membrane potential level of +7.3 .+-. 1.1 mV. The afterhyperpolarization disappeared in Na+-free or Ca2+-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. Unlike 5-HT voltage responses, which were biphasic in the majority of neurons 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. The initial depolarization induced by 5-HT seems 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 Ca2+. 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. The mean Hill coefficient obtained from the dose-response curves for the inward current induced by iontophoresis was 2.51 .+-. 0.14. Tetrodotoxin (0.2 .mu.M) blocked the soma action potential completely, but did not show any effect on 5-HT-induced responses. LSD and methysergide (1-100 .mu.M) had no depressant effect on the 5-HT-induced depolarization. (+)-Tubocurarine at low concentrations (1-5 .mu.M) inhibited the 5-HT induced inward current competitively. The mode of its inhibitory action became non-competitive at higher concentrations (10-20 .mu.M).