DIRECT EXCITATION OF RAT SPINAL MOTONEURONS BY SEROTONIN

1. The effects of serotonin (5‐HT) on visually identified motoneurones were investigated using the whole‐cell recording technique in a neonatal rat spinal cord slice preparation. 2. In current‐clamp recordings, bath application of 5‐HT depolarized motoneurones. This effect was observed after synaptic inputs were abolished by replacing external Ca2+ with Mg2+. 3. In voltage‐clamp recordings at holding potentials of ‐70 to ‐90 mV, 5‐HT induced an inward current (I5‐HT) in motoneurones in a Ca2(+)‐free‐Mg2+ solution containing tetrodotoxin. This inward current was accompanied by an increase in membrane conductance, which was prominent at voltages negative to the holding potential. 4. The inward I5‐HT response declined with repeated short applications of 5‐HT. I5‐HT produced by a single prolonged application (5 min) was only slightly diminished during the application period. 5. The minimum effective dose of 5‐HT for initiating the inward I5‐HT was less than 10 nM. At 10 microM, I5‐HT approached maximal levels. The averaged dissociation constant (Kd) for 5‐HT was approximately 120 nM. 6. Application of spiperone, the mixed 5‐HT1A, 5‐HT2 receptor antagonist, blocked the inward I5‐HT. Application of (+)‐8‐OH‐dipropylaminotetralin (8‐OHDPAT), a 5‐HT1A agonist, mimicked the action of 5‐HT. 7. Various K+ channel blockers including tetraethylammonium chloride (30 mM), 4‐aminopyridine (4 mM) and apamin (100 nM) did not abolish I5‐HT. Application of extracellular Cs+ (10 mM) blocked I5‐HT. 8. Peak inward I5‐HT became larger with increasing extracellular K+. With low Cl‐ pipette solution (less than 1 mM), or in low extracellular Na+ solution (26 mM), the inward I5‐HT was not abolished. 9. The current‐voltage relation of I5‐HT displayed inward rectification. In high external K+ concentration (20 mM), the reversal potential was about ‐29 mV, which is close to that of the inward rectifier evoked in motoneurones by membrane hyperpolarization. 10. The current generated by 5‐HT displayed similar characteristics to the inward rectifying current induced in motoneurones by membrane hyperpolarization. It is thus suggested that the 5‐HT‐induced current is possibly mediated by the intrinsic inward rectifier conductance. © 1990 The Physiological Society