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Glutamate-Mediated Extrasynaptic Inhibition: Direct Coupling of NMDA Receptors to Ca2+-Activated K+ Channels

Department of Neuroscience and The Neuroscience Graduate Program, School of Medicine, University of California, San Diego, La Jolla, CA 92093 USA
Neuron DOI:10.1016/S0896-6273(01)00428-7 pp.1027-1034

ABSTRACT NMDA receptors (NMDARs) typically contribute to excitatory synaptic transmission in the CNS. While Ca2+ influx through NMDARs plays a critical role in synaptic plasticity, direct actions of NMDAR-mediated Ca2+ influx on neuronal excitability have not been well established. Here we show that Ca2+ influx through NMDARs is directly coupled to activation of BK-type Ca2+-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.

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Keywords

BK-type Ca2+-activated K+ channels
 
glutamate uptake blockers
 
glutamatergic synapses
 
granule cells
 
IPSC
 
neuronal excitability
 
NMDA receptors
 
novel inhibitory action
 
olfactory bulb slices evokes
 
outside-out membrane patches
 
rat olfactory bulb granule cells
 
Repetitive stimulation
 
slow inhibitory postsynaptic current
 
slow IPSC
 
synaptic plasticity
 

Jeffry S Isaacson