Postsynaptic response to stimulation of the Schaffer collaterals with properties similar to those of synaptosomal aspartate release.
Aspartate satisfies all the criteria normally required for identification of a CNS neurotransmitter. Nevertheless, little electrophysiological evidence supports the existence of aspartate transmission. In studies with rat hippocampal synaptosomes, chemically evoked aspartate release differed from glutamate release in its relative sensitivity to increased Ca(2+) concentration outside the presynaptic active zones, inefficient coupling to P/Q-type Ca(2+) channels, sensitivity to KB-R7943, and resistance to native Clostridial toxins. We took advantage of these differences to search for a potential aspartate-mediated response at Schaffer collateral synapses in organotypic hippocampal slice cultures. The slice cultures were pretreated with botulinum neurotoxin C (BoNT/C) to eliminate most of the glutamate release so that an expectedly smaller aspartate-like component of the compound EPSC could be detected by whole cell patch clamp recording. In control cultures, NMDA receptor activation accounted for only 18% of the evoked EPSC and an NR2B-selective antagonist reduced the NMDA receptor-mediated component by only 20%. Block of P/Q-type Ca(2+) channels essentially eliminated the response and 0.1 muM KB-R7943 had no significant effect. In BoNT/C-pretreated cultures, however, NMDA receptor activation accounted for 77% of the evoked EPSC and an NR2B-selective antagonist reduced the NMDA receptor-mediated component by 57%. Block of P/Q-type Ca(2+) channels reduced the response by only 28%, but 0.1 muM KB-R7943 reduced it by 45%. These results suggest that part of the Schaffer collateral synaptic response has pharmacological properties similar to those of synaptosomal aspartate release and may therefore be mediated at least partly by released aspartate.
Zhang
Xuying
X
Department of Pharmacology, Box 3813, Duke University Medical Center, Durham, NC 27710, USA.
Nadler
J Victor
JV
D000818:Animals; D000831:Animals, Newborn; D001224:Aspartic Acid / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D020865:Calcium Channels, P-Type / Q000502:physiology; D020907:Calcium Channels, Q-Type / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D010636:Phenols / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D013569:Synapses / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*
D020865:Calcium Channels, P-Type; D020907:Calcium Channels, Q-Type; D018691:Excitatory Amino Acid Antagonists; D010636:Phenols; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; C109643:Ro 25-6981; D001224:Aspartic Acid; D002118:Calcium