Excitation of rat sympathetic preganglionic neurones by selective activation of the NK1 receptor

Abstract

Whole-cell current clamp recordings were made from 32 identified sympathetic preganglionic neurones (SPN) in neonatal rat thoracolumbar spinal cord slices. Perfusion of substance P (SP; 0.1–10μM) depolarised 7 out of 15 neurones tested and the selective NK₁ receptor agonist GR73632 (0.075–5 μM) depolarised 14 out of 24 neurones. The response to GR73632 could be maintained in the presence of tetrodotoxin (0.25–0.5 μM; n = 3) and was irreversibly reduced or abolished by the selective NK₁-receptor antagonist CP-99,994 (1–3 μM; n = 3). In 3 neurones, GR73632 evoked both a depolarising response and inhibitory postsynaptic potentials (IPSPs) and in the one neurone tested, the IPSPs were blocked by strychnine (20 μM), suggesting that NK₁ receptors may also be found upon inhibitory glycinergic interneurones. The application of either GR73632 or SP to a subpopulation of previously quiescent SPN evoked rhythmical oscillations in membrane potential (n = 6). These results indicate that the NK₁ receptor may play an important role in the regulation of both SPN and of inhibitory interneurones presynaptic to SPN.