The effects of neurokinin-1 receptor agonists on spinal motoneurones of the neonatal rat

The effects of substance P (SP) and the selective NK1 receptor agonist [Sar(9)Met(O-2)(11)] substance P on neonate rat spinal motoneurones were examined using intracellular recordings. Bath-administration of SP (0.1-3 mu M) or [Sar(9)Met(O-2)(11)] substance P (0.01-3 mu M) induced a tetrodotoxin (TTX)-insensitive (10 mu M) depolarization and a tetraethylammoniumchloride (TEA)-sensitive (3 mM) decrease in membrane conductance. The duration of the slow afterhyperpolarizations (AHPs) following the action potentials were significantly reduced (p = 0.003) by both NK1 receptor agonists. The mean duration of the sAHPs (+/-SEM) in control was 67.8 +/- 6.3 ms whereas in the presence of SP and [Sar(9)Met(O-2)(11)] substance P their duration was reduced to 41.7 +/- 4.6 ms. Low Ca2+ (0.2 mM)-containing artificial cerebrospinal fluid (ACSF) or addition of BaCl2 or CdCl2 (2 mM) reduced the durations of the slow AHPs by 55%. In the presence of these agents SP and [Sar(9)Met(O-2)(11)] substance P practically abolished the remaining slow AHPs, suggesting that the agonists also reduce a calcium-independent current. None of the effects induced by the NK1 receptor agonists were antagonized by the NK1 receptor antagonists (+/-)-CP-96;345 (10 mu M), RP 67580 (1 mu M) or GR 82334 (3-5 mu M). In conclusion this study demonstrates that SP and [Sar(9)Met(O-2)(11)] substance P elicit their effects on NK1 receptors by modulating at least two potassium currents, namely I-K and I-Ca(K). (C) 1996 Elsevier Science Ltd.