FGF-2 potentiates Ca(2+)-dependent inactivation of NMDA receptor currents in hippocampal neurons.
Peptide growth factors such as the neurotrophins and fibroblast growth factors have potent effects on synaptic transmission, development, and cell survival. We report that chronic (hours) treatment with basic fibroblast growth factor (FGF-2) potentiates Ca(2+)-dependent N-methyl-D-aspartate (NMDA) receptor inactivation in cultured hippocampal neurons. This effect is specific for the NMDA-subtype of ionotropic glutamate receptor and FGF-2. The potentiated inactivation requires ongoing protein synthesis during growth factor treatment and the activity of protein phosphatase 2B (PP2B or calcineurin) during agonist application. These results suggest a mechanism by which FGF-2 receptor signaling may regulate neuronal survival and synaptic plasticity.
Boxer
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Howard Hughes Medical Institute, New York University Medical Center, New York, New York 10016, USA.
Moreno
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Rudy
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Ziff
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D000185:Actinin / Q000502:physiology; D000818:Animals; D019703:Calcineurin / Q000378:metabolism; D002118:Calcium / Q000502:physiology*; D015220:Calcium Channels / Q000502:physiology; D002478:Cells, Cultured; D004558:Electric Stimulation; D004594:Electrophysiology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects*; D007150:Immunohistochemistry; D015640:Ion Channel Gating / Q000187:drug effects; D008564:Membrane Potentials / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D015220:Calcium Channels; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D016222:Fibroblast Growth Factor 2; D000185:Actinin; D019703:Calcineurin; D002118:Calcium