INSULIN POTENTIATES N-METHYL-D-ASPARTATE RECEPTOR ACTIVITY IN XENOPUSOOCYTES AND RAT HIPPOCAMPUS

Growth factor signal transduction pathways have recently been shown to affect voltage-gated ion channel activity. In this study we report th at insulin can modulate the activity of a ligand-gated ion channel, th e N-methyl-D-aspartate (NMDA) receptor. In Xenopus oocytes, brief insu lin exposure rapidly potentiated NR1a/NR2A and NR1a/NR2B receptor resp onses 2-3 fold and weakly potentiated NR1a/NR2C and NR1a/NR2D mediated -responses. Insulin potentiation of NR1a/NR2A receptor responses was s ignificantly blocked by staurosporine, suggesting kinase involvement i n insulin action. Insulin modulation of native NMDA receptors is sugge sted by the observation that insulin potentiated the NMDA receptor-med iated synaptic component in hippocampal slices. Regulation of NMDA rec eptor activity by growth factors may account for previous observations of growth factor modulation of central nervous system excitotoxicity.