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

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; 0.1-10 mu M) depolarised 7 out of 15 neurones tested and the selective NK1 receptor agonist GR73632 (0.075-5 mu M) depolarised 14 out of 24 neurones. The response to GR73632 could be maintained in the presence of tetrodotoxin (0.25-0.5 mu M; n = 3) and was irreversibly reduced or abolished by the selective NK1-receptor antagonist CP-99,994(1-3 mu M; 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 mu M), 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.