There is considerable evidence that glutamate is the principal neurotransmitter that mediates fast excitatory synaptic transmission in the vertebrate central nervous system1-3. This single transmitter seems to activate two or three distinct types of receptors, defined by their affinities for three selective structural analogues of glutamate, NMDA (N-methyl-D-aspartate), quisqualate and kainate1-6. All these agonists increase membrane permeability to monovalent cations7-9, but NMDA also activates a conductance that permits significant calcium influx 10,11 and is blocked in a voltage-dependent manner by extracellular magnesium12,13. Fast synaptic excitation seems to be mediated mainly by kainate/quisqualate receptors14-18, although NMDA receptors are sometimes activated 19-21. We have investigated the properties of these conductances using single-channel recording22 in primary cultures of hippocampal neurons, because the hippocampus contains all subtypes of glutamate receptors23,24 and because long-term potentiation of synaptic transmission occurs in this structure25,26. We find that four or more distinct single-channel currents are evoked by applying glutamate to each outside-out membrane patch. These conductances vary in their ionic permeability and in the agonist most effective in causing them to open. Clear transitions between all the conductance levels are observed. Our observations are compatible with the model that all the single channel conductances activated by glutamate reflect the operation of one or two complex molecular entities.
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