The role of excitatory amino acid receptors in regulating excitability of sympathetic preganglionic neurones
The role of excitatory amino acid receptors in the regulation of excitability of sympathetic preganglionic neurones was investigated. Whole-cell patch-clamp recordings were made from sympathetic preganglionic neurones in transverse slices of the rat (8 to 14 days). Sympathetic preganglionic neurones were identified by their characteristic membrane properties and morphology. Perfusion of α-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid (AMPA; 1 to 10 μM; n = 25), kainate (10 to 50 μM; n = 66), and domoic acid (0.5 to 10 μM; n = 10) evoked concentration-dependent excitatory depolarisation in all SPNs tested. Domoic acid was significantly more potent on sympathetic preganglionic neurones than either AMPA or kainate. Responses to AMPA were reduced by 6-cyano-7-nitroquinoxaline-2, 3-dione (CNQX; 10 μM) and completely abolished by GYKI 52466 (50 μM). By contrast responses to kainate and domoic acid were reduced by CNQX (10 μM) and reduced but not abolished by GYKI 52466 (50 μM). Cyclothiazide (100 μM) selectively potentiated AMPA-induced responses and Concanavalin A selectively potentiated kainate-induced responses in sympathetic preganglionic neurones. Excitatory postsynaptic potentials (EPSPs) were evoked in sympathetic preganglionic neurones by electrical stimulation of the lateral funiculus. EPSPs were differentially sensitive to GYK1 52466 and CNQX suggesting a differential role for AMPA and kainate receptors in sympathetic preganglionic neurones. These results demonstrate that non-NMDA receptors, which form pharmacologically distinct AMPA and kainate receptor populations, are found on sympathetic preganglionic neurones. Domoic acid appears to excite sympathetic preganglionic neurones via kainate receptors. Differential roles were also discovered for AMPA and kainate receptors in synaptic transmission.