PMID: 8943079Nov 26, 1996Paper

Interactions between two divalent ion binding sites in N-methyl-D-aspartate receptor channels

Proceedings of the National Academy of Sciences of the United States of America
G Sharma, C F Stevens

Abstract

N-methyl-D-aspartate receptor channels exhibit a high permeability for calcium ions. In this report, we confirm that calcium ions permeate effectively through the wild-type channels, and find that their presence within the pore blocks the flux of sodium and other ions. Further proof for this ionic block comes from the analysis of the epsilon 1(N614Q) mutation where the high permeability of calcium is unchanged but the block by calcium ions is increased twofold. In both the wild-type and mutant channels, calcium ion block is independent of membrane voltage; therefore, the calcium binding site is outside the voltage gradient through the pore and must be close to the extracellular mouth of the ion conductance pathway. This calcium site is distinct from the magnesium binding site, which lies 80% into the pore's electrostatic field and thus exhibits a marked voltage dependence of binding. The epsilon 1(N614Q) mutation reduces the affinity of magnesium ion for its binding site but increases the affinity of calcium ion for its binding site. Since a single mutation perturbs two distinct binding sites in opposite ways, we postulate that binding of divalent ions at the two sites interact.

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Aug 20, 1996·Proceedings of the National Academy of Sciences of the United States of America·G Sharma, C F Stevens

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Aug 28, 1999·Progress in Neurobiology·T Yamakura, K Shimoji
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Nov 10, 1998·The Journal of General Physiology·L P Wollmuth, B Sakmann
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Feb 27, 2001·The Journal of General Physiology·Y Zhu, A Auerbach
Aug 19, 2010·Pharmacological Reviews·Stephen F TraynelisRay Dingledine
Dec 10, 1999·Proceedings of the National Academy of Sciences of the United States of America·S M Antonov, J W Johnson
Dec 3, 2013·European Journal of Pharmacology·Yuriy Pankratov, Ulyana Lalo
Oct 22, 2008·The Journal of Physiology·Richard J Clarke, Jon W Johnson
Jan 5, 2002·The Journal of Physiology·Claudia JatzkeLonnie P Wollmuth
Oct 29, 2014·The Journal of General Physiology·Bruce A Maki, Gabriela K Popescu
Jun 4, 1999·Biophysical Journal·R C AranedaM V Bennett
Jul 17, 2013·Best Practice & Research. Clinical Endocrinology & Metabolism·Edward M Brown
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Jan 5, 2002·Mental Retardation and Developmental Disabilities Research Reviews·O P MishraM Delivoria-Papadopoulos
Jul 25, 2018·The Journal of General Physiology·Kasper B HansenStephen F Traynelis
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