An electrophysiological study into the actions of neurokinins upon sympathetic preganglionic neurones in vitro
This study has investigated the role of neurokinin receptors, in particular the NK-1 receptor, in the regulation of excitability of SPN using selective agonists and antagonists. The whole-cell patch clamp technique was used to record from SPN in transverse slices of neonatal rat spinal cord in vitro. Neurones were positively identified as SPN due to their characteristic electrophysiological and morphological properties. Perfusion of the selective NK-1 receptor agonist GR73632 (25 nM-5μM; 2-120 s) induced concentration-dependent depolarising responses in SPN. The response to GR73632 (67% of SPN responsive) was maintained in the presence of TTX (250-500 nM), suggesting that NK-1 receptors are located directly upon SPN. The depolarising response to GR73632 was associated with an increase in neuronal input resistance, reduced with increasing membrane hyperpolarisation, and blocked by two selective NK-1 receptor antagonists, CP-99,994 (1-3 μM) and GR82334 (250 nM-1 μM). Excitatory postsynaptic potentials and strychnine-sensitive inhibitory postsynaptic potentials were also induced by GR73632 in approximately 10% of neurones. Application of GR73632 to a subpopulation of silent SPN induced rhythmical oscillations in membrane potential. The induction of oscillations following NK-1 receptor activation can lead to synchronised action potential firing within groups of SPN. This study has presented preliminary evidence to suggest that a presynaptic NK-1 receptor may exist upon the terminals of neurones which descend from supraspinal centres in synapse upon SPN. Activation of this subtype of NK-1 receptor was found to exert an inhibitory influence upon glutamatergic synaptic transmission to SPN. The results from this study suggest that activation of the NK-1 receptor may have a major excitatory effect upon the activity of SPN, probably by causing the closure of potassium channels open at rest.