Low-affinity kainate receptors and long-lasting depression of NMDA-receptor-mediated currents in rat superficial dorsal horn.
In an in vitro spinal cord slice preparation whole cell electrophysiological recordings of rat superficial dorsal horn neurons responding differentially to glutamate (Glu) and N-methyl-D-aspartate (NMDA) were investigated systematically for the role of kainate (KA) receptors in modulating their activity. In these neurons, coapplication of Glu and NMDA, as well as application of Glu immediately before NMDA, induced long- and short-lasting depressions of NMDA-induced currents as well as depression of NMDA-receptor-mediated excitatory postsynaptic currents. KA applied before NMDA mimicked Glu-induced attenuating effects. Furthermore, the low-affinity KA receptor antagonist 5-nitro-6,7,8,9- tetrahydrobenzo[G]indole-2,3-dione-3-oxime potentiated Glu-induced NMDA-receptor-mediated currents in neurons responding differentially to Glu and NMDA. These results provide evidence for a novel mechanism, which may relate to classical long-term depression, involving low-affinity KA receptors in long-lasting modulation of NMDA-receptor-mediated currents. This implies a physiological role of KA receptors in long-term modulation of sensory transmission in the superficial dorsal horn of rat spinal cord.
Sequeira
S
S
Department of Cellular and Molecular Pharmacology, Discovery Division, Astra Pain Control AB, S-141 57 Huddinge, Sweden.
Näsström
J
J
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D004594:Electrophysiology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000166:cytology / Q000502:physiology; D018698:Glutamic Acid / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D009475:Neurons, Afferent / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D018696:Neuroprotective Agents / Q000494:pharmacology; D010091:Oximes / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018092:Kainic Acid Receptors / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D013116:Spinal Cord / Q000166:cytology* / Q000502:physiology; D013126:Spinal Nerve Roots / Q000166:cytology / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D002118:Calcium; D003515:Cycloleucine; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018698:Glutamic Acid; D007211:Indoles; D007608:Kainic Acid; D016202:N-Methylaspartate; D018696:Neuroprotective Agents; D010091:Oximes; D011810:Quinoxalines; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; C036361:1-amino-1,3-dicarboxycyclopentane; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; C084273:5-nitro-6,7,8,9-tetrahydrobenzo(G)indole-2,3-dione-3-oxime