The Biochemistry of Copper in Man and Its Role in the Pathogenesis of Wilson’s Disease (Hepatolenticular Degeneration)

Walshe, J. M.

doi:10.1007/978-1-4684-1956-6_4

Cited by 4 publications

(1 citation statement)

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“…In man, Wilson's disease or hepatolenlicular degeneration, a metabolic disorder characterized by dysfunction of copper transport and storage, is clinically characterized by neurological disturbances: muscular rigidity, tremor and dyscoordination of movement; by abnormalities in liver and renal function; and by visible deposits of copper in the cornea (for review see Walshe, 1972). An increased copper content is present in almost all areas of the brain, with up to a ten-fold excess copper concentration above normal values (for review see Thompson and Cumings, 1957).…”

Section: Introductionmentioning

confidence: 99%

Copper Modulation of NMDA Responses in Mouse and Rat Cultured Hippocampal Neurons

Vlachová

Zemková

Vyklický

1996

Eur J of Neuroscience

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The effect of Cu2+ on NMDA receptors was studied in cultured mouse and rat hippocampal neurons using whole-cell patch-clamp and a fast perfusion system. Analysis of the Cu2+ concentration-response curve for inhibition of NMDA-induced currents suggests that free Cu2+ directly inhibits NMDA receptors with an IC50 of 0.27 microM. Cu2+ was ineffective in blocking NMDA receptor activity when complexed with NMDA or glycine; NMDA-Cu2+ and glycine-Cu2+ complexes acted as agonists of similar potency to the free amino acids. The inhibition by Cu2+ (10-100 microM) of responses to 10 microM NMDA was essentially voltage-independent. The onset of inhibition by 100 microM Cu2+ of responses to 2 microM glutamate acting at NMDA receptors was significantly faster than NMDA receptor deactivation evoked by a sudden decrease in the concentration of glycine or glutamate, or of both agonists. This suggests that Cu2+ acts as a non-competitive antagonist, and does not directly interfere with the binding of glutamate or glycine to their recognition sites on the NMDA receptor complex. In the absence of NMDA the apparent association rate constant for binding of Cu2+ to NMDA receptors, calculated from the rate of onset of block by Cu2+ of test responses to NMDA, was 19 times slower than in the presence of 30 microM NMDA, suggesting that Cu2+ interacts preferentially with agonist-bound receptors. Our results show that Cu2+ is a potent inhibitor of NMDA receptor-mediated responses.

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Section: Introductionmentioning

confidence: 99%