snx-230 and iberiotoxin

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.

Topics: Animals; Calcium; Calcium Channel Blockers; Calcium Channels; Evoked Potentials; Excitatory Postsynaptic Potentials; Glutamic Acid; Ion Channel Gating; Ion Transport; Large-Conductance Calcium-Activated Potassium Channels; Macromolecular Substances; Membrane Potentials; Models, Neurological; Nerve Tissue Proteins; Neuronal Plasticity; Nicardipine; Olfactory Bulb; Olfactory Receptor Neurons; omega-Conotoxin GVIA; omega-Conotoxins; Patch-Clamp Techniques; Peptides; Potassium; Potassium Channels; Potassium Channels, Calcium-Activated; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate; Smell