Abstract
The effects of substance P (SP) and the selective NK 1 receptor agonist [Sar 9Met(O 2) 11] substance P on neonate rat spinal motoneurones were examined using intracellular recordings. Bath-administration of SP (0.1–3 μM) or [Sar 9Met(O 2) 11] substance P (0.01–3 μM) induced a tetrodotoxin (TTX)-insensitive (10 μM) 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 NK 1 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 9Met(O 2) 11] substance P their duration was reduced to 41.7 ± 4.6 ms. Low Ca 2+ (0.2 mM)-containing artificial cerebrospinal fluid (ACSF) or addition of BaCl 2 or CdCl 2 (2 mM) reduced the durations of the slow AHPs by 55%. In the presence of these agents SP and [Sar 9Met(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 NK 1 receptor agonists were antagonized by the NK 1 receptor antagonists (±)-CP-96,345 (10 μM), RP 67580 (1 μM) or GR 82334 (3–5 μM). In conclusion this study demonstrates that SP and [Sar 9Met(O 2) 11] substance P elicit their effects on NK 1 receptors by modulating at least two potassium currents, namely I K and I Ca( K) .
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call