Metabotropic regulation of intrinsic excitability by synaptic activation of kainate receptors.
Prolonged modification of intrinsic neuronal excitability is gaining prominence as an activity-dependent form of plasticity. Here we describe a potential synaptic initiation mechanism for these changes in which release of the transmitter glutamate acts on kainate receptors to regulate the postspike slow afterhyperpolarization (sAHP). This action of synaptically released glutamate was occluded by previous kainate application. Furthermore, inhibition of glutamate uptake enhanced the effects of synaptic activation. Glutamate-mediated kainate receptor inhibition of sAHP current (I(sAHP)) was blocked by the PKC inhibitor calphostin C, confirming the requirement for a metabotropic signaling cascade. These data describe a new physiological function for glutamate release: activation of metabotropic kainate receptors, which control directly the excitability of pyramidal cells and probably contribute to prolonged excitability changes.
Melyan
Zare
Z
Neuroscience Group, School of Biological Sciences, University of Southampton, Southampton SO16 7PX, United Kingdom.
Lancaster
Barrie
B
Wheal
Howard V
HV
D000818:Animals; D001224:Aspartic Acid / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D009281:Naphthalenes / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D018092:Kainic Acid Receptors / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013569:Synapses / Q000378:metabolism*
D001224:Aspartic Acid; D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D018698:Glutamic Acid; D009281:Naphthalenes; D011493:Protein Kinase C; D018092:Kainic Acid Receptors; C120673:benzyloxyaspartate; C058819:calphostin C