MODULATION OF AMPA KAINATE RECEPTORS IN CULTURED MURINE HIPPOCAMPAL-NEURONS BY PROTEIN-KINASE-C

1. The patch clamp technique, together with intracellular perfusion of the catalytic fragment of protein kinase C (PKCM), was employed to in vestigate the role of this enzyme in the intracellular regulation of a lpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)/kainate re ceptors in cultured hippocampal neurones. 2. The responses evoked by n ear-maximal concentrations of kainate (250 muM) and AMPA (100 muM) wer e potentiated by the introduction of PKCM, whilst co-application of th e inhibitory peptide fragment PKCI(19-36) prevented this action. 3. Mo dulation of kainate responses by PKCM was dependent upon the concentra tion of agonist applied. Currents evoked by kainate were potentiated a t concentrations above those which caused 50% of the maximal response (EC50) and depressed at lower concentrations. Furthermore, okadaic aci d, a specific inhibitor of phosphatases 1 and 2A, had a similar effect upon concentration-response relationships when currents activated by kainate were recorded using the perforated patch technique. 4. In addi tion, the mean amplitude and/or time constant of decay of miniature ex citatory synaptic currents (mediated by AMPA/kainate receptors) was in creased by the intracellular injection of PKCM. 5. These observations suggest that the function of postsynaptic excitatory amino acid recept ors can be modulated by the activity of PKC as well as by endogenous p hosphatases. This regulation may contribute to some forms of synaptic plasticity within the central nervous system.