Glutamate-mediated extrasynaptic inhibition: Direct coupling of NMDA receptors to Ca2+-activated K+ channels

NMDA receptors (NMDARs) typically contribute to excitatory synaptic transmi ssion in the CNS. While Ca2+ influx through NMDARs plays a critical role in synaptic plasticity, direct actions of NMDAR-mediated Ca2+ influx on neuro nal excitability have not been well established. Here we show that Ca2+ inf lux through NMDARs is directly coupled to activation of BK-type Ca2+-activa ted K+ channels in outside-out membrane patches from rat olfactory bulb gra nule cells. Repetitive stimulation of glutamatergic synapses in olfactory b ulb slices evokes a slow inhibitory postsynaptic current (IPSC) in granule cells that requires both NMDARs and BK channels. The slow IPSO is enhanced by glutamate uptake blockers, suggesting that extrasynaptic NMDARs underlie the response. These findings reveal a novel inhibitory action of extrasyna ptic NMDARs in the brain.