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  Intracellular Mg2+ interacts with structural determinants of the narrow constriction contributed by the NR1-subunit in the NMDA receptor channel

Wollmuth, L. P., Kuner, T., & Sakmann, B. (1998). Intracellular Mg2+ interacts with structural determinants of the narrow constriction contributed by the NR1-subunit in the NMDA receptor channel. Journal of Physiology-London, 506(1), 33-52. doi:10.1111/j.1469-7793.1998.00033.x.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-002B-9AE4-4 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-002B-9AE5-2
Genre: Journal Article
Alternative Title : Intracellular Mg2+ interacts with structural determinants of the narrow constriction contributed by the NR1-subunit in the NMDA receptor channel

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 Creators:
Wollmuth, Lonnie P.1, Author              
Kuner, Thomas1, 2, Author              
Sakmann, Bert1, Author              
Affiliations:
1Department of Cell Physiology, Max Planck Institute for Medical Research, Max Planck Society, ou_1497701              
2Department of Molecular Neurobiology, Max Planck Institute for Medical Research, Max Planck Society, ou_1497704              

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 Abstract: 1. N-methyl-D-aspartate (NMDA) receptor channels are blocked by intracellular Mg2+ in a voltage-dependent manner. Amino acid residues positioned at or near the narrow constriction that interact with intracellular Mg2+ were identified in recombinant NR1-NR2A channels expressed in Xenopus oocytes or human embryonic kidney (HEK) 293 cells. 2. In the absence of extracellular Ca2+, the block of wild-type channel by intracellular Mg2+ measured using macroscopic currents showed a voltage dependence (delta) of around 0.38 and a voltage-independent affinity for the channel of 4 mM. These parameters were independent of the Mg2+ concentration (0.05-10mM), and were indistinguishable from those found for the reduction of single channel amplitudes under the same ionic conditions. Under bionic conditions with high intracellular Mg2+ and K+ extracellularly, Mg2+ was weakly permeant. Mg2+ efflux, however, attenuated the block only at positive potentials (> +80 mV). 3. Substitutions of the N-site asparagine in the NR1-subunit altered intracellular Mg2+ block over physiological membrane potentials (+10 to +50 mV). Substitution of glycine, glutamine or serine attenuated the extent of block whereas the negatively charged aspartate enhanced it, consistent with the side chain of the native asparagine at this position contributing to a blocking site for intracellular Mg2+. 4. Substitutions of the N-site or N + 1 site asparagine in the NR2A-subunit, which form a blocking site for extracellular Mg2+, also altered the block by intracellular Mg2+. However, for the NR2A-subunit N-site asparagine, the block was reduced but only at non-physiological high potentials (> +70 mV). 5. The NR2A-subunit N + 1 site asparagine, which together with NR1-subunit N-site asparagine forms the narrow constriction of the channel, also contributed to a blocking site for intracellular Mg2+. However, it did so to lesser extent than the NR1-subunit N-site and in a manner different from its contribution to a blocking site for extracellular Mg2+. 6. It is concluded that intracellular Mg2+ interacts with residues that form the narrow constriction in the NMDA receptor channel with the N-site asparagine of the NR1-subunit representing the dominant blocking site. Thus, intracellular Mg2+ interacts with different asparagine residues at the narrow constriction than extracellular Mg2+, although the two blocking sites are positioned very close to each other.

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Language(s): eng - English
 Dates: 1997-09-121997-01-101997-09-121998-01-01
 Publication Status: Published in print
 Pages: 20
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
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Title: Journal of Physiology-London
  Other : J. Physiol.-London
Source Genre: Journal
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Publ. Info: London : Cambridge University Press
Pages: - Volume / Issue: 506 (1) Sequence Number: - Start / End Page: 33 - 52 Identifier: ISSN: 0022-3751
CoNE: https://pure.mpg.de/cone/journals/resource/954925334693_1