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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 doseresponse 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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