NMDA-Dependent modulation of hippocampal kainate receptors by calcineurin and Ca(2+)/calmodulin-dependent protein kinase.
Neurotransmitter receptor function can be influenced by the phosphorylation state of the receptor or of associated proteins. Here we show that kainate receptors expressed in cultured hippocampal neurons can be modulated by Ca(2+)/calmodulin-dependent phosphatase (calcineurin) and Ca(2+)/calmodulin-dependent kinase (CaMK). Ca(2+) influx through NMDA receptor or voltage-sensitive calcium channels resulted in a transient depression of the kainate receptor current. This calcium-induced depression of the kainate receptor current depended on the activation of the phosphatase calcineurin. The amplitude of the kainate receptor currents returned to the baseline level in approximately 9 sec (tau = 3.6 sec), and the recovery of the current amplitude depended on CaMK activity. The effect on kainate receptor currents was dependent on the frequency of NMDA receptor activation. Although low-frequency (0.1 Hz) NMDA application induced depression followed by recovery of the kainate receptor currents, higher frequency (1 Hz) NMDA applications induced a more prolonged depression. Kainate receptors have been shown to modulate synaptic transmission by both presynaptic and postsynaptic mechanisms. Our results suggest that synaptic activity mediated by NMDA receptors, or other routes of Ca(2+) influx, may, in turn, modulate the function of kainate receptors.
Ghetti
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Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.
Heinemann
S F
SF
D000818:Animals; D000831:Animals, Newborn; D019703:Calcineurin / Q000187:drug effects / Q000502:physiology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D007608:Kainic Acid / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D018092:Kainic Acid Receptors / Q000187:drug effects / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology*
D019703:Calcineurin; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D007608:Kainic Acid; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate