ENHANCEMENT OF THE N-METHYL-D-ASPARTATE RESPONSE IN SPINAL DORSAL HORN NEURONS BY CAMP-DEPENDENT PROTEIN-KINASE

Glutamate-gated ion channels mediate excitatory synaptic transmission in the central nervous system and are involved in synaptic plasticity, neuronal development and excitotoxicity (5,24). These ionotropic glut amate receptors were classified according to their preferred agonists as AMPA lpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid), KA ( kainate), and NMDA (N-methyl-D-aspartate) receptors [Trends Pharmacol. Sci., 11 (1990) 25-33]. The present study of NMDA receptor channels e xpressed in acutely isolated spinal dorsal horn (DH) neurons of young rat reveals that they are subject to modulation through the adenylate cyclase cascade. Whole-cell voltage-clamp recording mode was used to e xamine the effect of adenosine 3',5'-monophosphate (cAMP)-dependent pr otein kinase (PKA) on the responses of DH neurons to NMDA. Whole-cell current response to NMDA was enhanced by 8 Br-cAMP, a membrane permean t analog of cAMP or by intracellular application of cAMP or catalytic subunit of PKA.