Modulation of respiratory activity of neonatal rat phrenic motoneurones by serotonin

1. The effects of serotonin on phrenic motoneurones were studied in an in vitro preparation of the isolated brainstem and spinal cord from neonatal rats. 2. Serotonin (5-HT; > or = 5-10 microM) increased inspiratory-modulated phrenic nerve activity and produced a small amount of tonic activity during expiration. Inspiratory-modulated activity of the fourth cervical ventral root also increased, but was accompanied by robust tonic activity, which often obscured the rhythmic activity. 3. Serotonin, in both normal and tetrodotoxin-containing medium, depolarized phrenic motoneurones and increased cell input resistance. Serotonin also increased inspriatory-modulated firing as well as the response of phrenic motoneurones to injected current. The y-intercept of the relationship between firing frequency and injected current (f-I) was increased, but the slope was not affected. There was no bistable firing behaviour. 4. Under voltage clamp conditions, 5-HT produced a tonic inward current of 0.07-0.37 nA. This current increased with less negative holding potentials and decreased with more negative holding potentials (-75 to -90 mV) but did not reverse. 5. In addition, 5-HT decreased inspiratory-modulated synaptic current by 23 +/- 6%. The degree of attenuation was not affected by holding potential. The time course of the decrease in inspiratory-modulated synaptic current was similar to the changes seen in tonic inward current and input resistance. 6. Depolarization, tonic inward current, and shift in the f-I relationship produced by 5-HT were antagonized by the 5-HT2/1C receptor antagonist ketanserin and mimicked by the 5-HT2/1C agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl (DOI). However, the 5-HT induced decrease in inspiratory-modulated synaptic current was not reduced by ketanserin nor mimicked by DOI. 7. We conclude that exogenously applied 5-HT simultaneously increases cell excitability and decreases inspiratory-modulated synaptic current in phrenic motoneurones via different types of receptors. When these responses occurred simultaneously, the increase in excitability predominated and the net effect was an augmentation of inspiratory-modulated phrenic motoneurone activity.