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J Physiol Vol 323 pp 543-567
Copyright © 1982 by The Physiological Society
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5-Hydroxytryptamine receptors of visceral primary afferent neurones on rabbit nodose ganglia

H. Higashi and S. Nishi

Department of Physiology, Kurume University, School of Medicine, Kurume 830, Japan

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 µM) 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 Ca2+-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 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.

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 Ca2+.

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 µM) 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 µM) had no depressant effect on the 5-HT-induced depolarization.

11. (+)-Tubocurarine at low concentrations (1-5 µM) inhibited the 5-HT induced inward current competitively. The mode of its inhibitory action became noncompetitive at higher concentrations (10-20 µM).




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