INHIBITION OF SYMPATHETIC PREGANGLIONIC NEURONS BY SPINAL GLYCINERGICINTERNEURONS

Intracellular and whole-cell patch-clamp recordings were obtained from sympathetic preganglionic neurons in rat spinal cord slices. Perfusio n of selective ionotropic and metabotropic excitatory amino acid agoni sts induced depolarizing responses in all neurons. In approximately 20 % of neurons the application of these agonists also evoked inhibitory postsynaptic potentials. The application of the ionotropic receptor an tagonist 6-cyano-7-nitroquinoxaline-2,3-dione (5-40 mu M) blocked the inhibitory postsynaptic potential discharges induced by lpha-amino-3-h ydroxy-5-methyl-4-isoxazolepropionic acid (0.5-50 mu M) and N'-methyl- D-aspartate (0.5-50 mu M), but failed to block the inhibitory postsyna ptic potentials induced by quisqualate (0.5-50 mu M) and (1S,3R)-1-ami nocyclopentane-1,3-dicarboxylic acid (10-200 mu M). Similar inhibitory postsynaptic potentials were seen to occur spontaneously or could be evoked by electrical stimulation of the dorsal horn. The application o f tetrodotoxin blocked the spontaneous and evoked inhibitory postsynap tic potential, indicating that they result from activity-dependent rel ease of neurotransmitter. Strychnine antagonized all inhibitory postsy naptic potentials suggesting that they were mediated via glycine recep tors. The reversal potential of the inhibitory postsynaptic potentials was -65 mV for intracellular and -55 mV for whole-cell recordings. Th is latter value is dose to the reversal potential for chloride, sugges ting that the inhibitory postsynaptic potentials were mediated by a ch loride conductance. Perfusion of glycine (0.1-1 mM) induced inhibitory hyperpolarizing responses in the majority of neurons. This hyperpolar izing response was associated with a reduction in neuronal input resis tance, persisted in the presence of tetrodotoxin, was blocked by stryc hnine and reversed at -55 mV. In some neurons, glycine induced a membr ane depolarization and increased the rate of spontaneous action potent ial firing. This excitatory effect of glycine was blocked by tetrodoto xin, showed Voltage dependency and was less sensitive to strychnine th an the glycine-induced inhibitory response. We conclude from these dat a that spinal interneurons which synapse with sympathetic preganglioni c neurons can be activated through multiple subtypes of excitatory ami no acid receptor, including both ionotropic and metabotropic receptors . These interneurons release glycine to evoke inhibitory postsynaptic potentials which are mediated via a strychnine-sensitive glycine recep tor coupled to a chloride conductance.