Selective effects of cyanide (100 microM) on the excitatory amino acid-induced elevation of intracellular calcium levels in neuronal culture.
The effect of low concentrations of cyanide on the excitatory amino acid-induced elevations of intracellular calcium levels ([Ca2+]i) was studied in cerebellar granule cells using ratio fluorometry with fura-2. Glutamate, kainate, N-methyl-D-aspartate (NMDA), quisqualate (50 microM, each) and membrane depolarization by 40 mM KCl caused elevations of [Ca2+]i which were 10-, 10-, 3-, 2.3-, 10-fold over baseline levels, respectively. Cyanide, 100 microM, greatly augmented the increases in [Ca2+]i induced by glutamate, kainate and NMDA but not those induced by quisqualate or KCl. In the absence of these excitatory amino acids, cyanide had no significant effect in concentrations up to 400 microM. Elevations of [Ca2+]i induced by quisqualate and KCl were not significantly augmented by higher concentrations of cyanide (400 microM). Selective antagonists could block the effect of cyanide+the respective agonist; however, the calcium channel blockers, lanthanum and diltiazem lowered both NMDA- and kainate-induced elevations of [Ca2+]i, yet neither blocked increases in calcium when 100 microM cyanide was added. Collectively, these data support an interaction of cyanide with the excitatory amino acid receptor.
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Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson 39216-4505.
McCaslin
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D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D004110:Diltiazem / Q000494:pharmacology; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D007608:Kainic Acid / Q000494:pharmacology; D007811:Lanthanum / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D011189:Potassium Chloride / Q000494:pharmacology; D016318:Quisqualic Acid / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012966:Sodium Cyanide / Q000494:pharmacology*
D000596:Amino Acids; D005971:Glutamates; D018698:Glutamic Acid; D016202:N-Methylaspartate; D011189:Potassium Chloride; D007811:Lanthanum; D016318:Quisqualic Acid; D004110:Diltiazem; D012966:Sodium Cyanide; D007608:Kainic Acid; D002118:Calcium