Induction of cobalt accumulation by excitatory amino acids within neurons of the hippocampal slice.
Computer-assisted image analysis was used to establish the dose response of excitatory amino acid (EAA) analogs on the induction of cobalt accumulation within pyramidal and granule cell neurons in 400 microns slices of gerbil hippocampus. Slices were incubated 20 min at 22 degrees C in a solution containing 5 mM CoCl2 and 0-1,000 microM EAA analog. The cobalt was visualized by development in (NH4)2S, and the slices were digitized for quantitative densitometry. Kainic acid (KA) had the largest effect and induced cobalt accumulation in the dentate gyrus and CA1, 180% and 150% above control, respectively, with an ED50 = 30 microM. alpha-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) induced accumulations of cobalt in CA1 and hilar neurons 130% above control with an ED50 = 30 microM, but had little effect on dentate granule cells. The accumulations induced by KA and AMPA were blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), but not by DL-2-amino-5-phosphonovaleric acid (AP5) or voltage-dependent calcium channel blockers. N-Methyl-D-aspartate (NMDA) induced accumulation in the dentate and CA1 150% above control in a pattern similar to KA, but with an ED50 of 100 microM. The accumulation was blocked by both AP5 and CNQX. These data indicate that cobalt-permeable, receptor-activated divalent cation channels are differentially distributed within the gerbil hippocampus, and have differential sensitivities to non-NMDA agonists. The localization of KA-activated, cobalt-permeable channels appears to be coincident with the flop form of the AMPA-selective calcium-permeable glutamate receptor-activated channel.(ABSTRACT TRUNCATED AT 250 WORDS)
Williams
L R
LR
CNS Diseases Research, Upjohn Company, Kalamazoo, MI 49001.
Pregenzer
J F
JF
Oostveen
J A
JA
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D003035:Cobalt / Q000378:metabolism*; D005849:Gerbillinae; D006624:Hippocampus / Q000378:metabolism*; D007051:Ibotenic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D066298:In Vitro Techniques; D007608:Kainic Acid / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
D007051:Ibotenic Acid; D003035:Cobalt; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D007608:Kainic Acid