Functional N-Methyl-D-Aspartate and Non-N-Methyl-D-Aspartate Receptors are Expressed by Rat Supraoptic Neurosecretory...

Abstract A considerable amount of evidence has accumulated to support a role for excitatory glutamatergic transmission in the regulation of the hypothalamo-neurohypophysial system. Glutamate immunoreactivity has been found in axon terminals forming asymmetric synapses on to magnocellular neurosecretory cells and kynurenic acid, a broad spectrum glutamate receptor antagonist inhibits 1) spontaneous electrical activity in vivo, 2) excitatory postsynaptic potentials in hypothalamic slices, and 3) osmotically-evoked vasopressin release from hypothalamic explants. While this provides strong evidence for glutamatergic regulation of hypothalamic magnocellular neurosecretory cells, the subtypes of glutamate receptors expressed by these cells have not been defined. We have, therefore, obtained current and voltage clamp recordings from supraoptic magnocellular neurosecretory cells in vitro to investigate the functional and pharmacological properties of their glutamate receptors. Application of micromolar concentrations of L-glutamate, or of the agonists kainate, quisqualate and N-methyl-D-aspartate (NMDA), produced reversible and dose-dependent depolarizations in all cells tested. These responses were mediated by postsynaptic receptors since they persisted during chemical synaptic blockade with Ca(2 +) -free or tetrodotoxin-containing solutions. The inward current induced by NMDA showed a marked Mg(2+)-sensitive voltage dependence, and was blocked by D, L-2-amino-5-phosphonovalerate. In contrast, currents induced by kainate and quisqualate showed linear current-voltage properties and were antagonized by 6-cyano-7-nitroquinoxaline-2,3-dione. We conclude that both NMDA and non-NMDA receptors are expressed by magnocellular neurosecretory cells of the rat supraoptic nucleus.