Glutamate-mediated extrasynaptic inhibition: direct coupling of NMDA receptors to Ca(2+)-activated K+ channels.
NMDA receptors (NMDARs) typically contribute to excitatory synaptic transmission in the CNS. While Ca(2+) influx through NMDARs plays a critical role in synaptic plasticity, direct actions of NMDAR-mediated Ca(2+) influx on neuronal excitability have not been well established. Here we show that Ca(2+) influx through NMDARs is directly coupled to activation of BK-type Ca(2+)-activated K+ channels in outside-out membrane patches from rat olfactory bulb granule cells. Repetitive stimulation of glutamatergic synapses in olfactory bulb slices evokes a slow inhibitory postsynaptic current (IPSC) in granule cells that requires both NMDARs and BK channels. The slow IPSC is enhanced by glutamate uptake blockers, suggesting that extrasynaptic NMDARs underlie the response. These findings reveal a novel inhibitory action of extrasynaptic NMDARs in the brain.
Isaacson
J S
JS
Department of Neuroscience, School of Medicine, University of California San Diego, La Jolla, CA 92093, USA. jisaacson@ucsd.edu
Murphy
G J
GJ
D000818:Animals; D002118:Calcium / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D005071:Evoked Potentials / Q000187:drug effects*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D018698:Glutamic Acid / Q000494:pharmacology*; D015640:Ion Channel Gating / Q000187:drug effects; D017136:Ion Transport / Q000187:drug effects; D051036:Large-Conductance Calcium-Activated Potassium Channels; D046911:Macromolecular Substances; D008564:Membrane Potentials / Q000187:drug effects; D008959:Models, Neurological; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D009529:Nicardipine / Q000494:pharmacology; D009830:Olfactory Bulb / Q000166:cytology* / Q000502:physiology; D018034:Olfactory Receptor Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels / Q000502:physiology*; D024681:Potassium Channels, Calcium-Activated; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology*; D012903:Smell / Q000502:physiology; D020866:omega-Conotoxin GVIA / Q000494:pharmacology; D020960:omega-Conotoxins / Q000494:pharmacology
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D051036:Large-Conductance Calcium-Activated Potassium Channels; D046911:Macromolecular Substances; D009419:Nerve Tissue Proteins; D010455:Peptides; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D016194:Receptors, N-Methyl-D-Aspartate; D020960:omega-Conotoxins; C075851:omega-conotoxin-MVIIC; D018698:Glutamic Acid; C064719:iberiotoxin; D020866:omega-Conotoxin GVIA; D009529:Nicardipine; D011188:Potassium; D002118:Calcium