K+ occupancy of the N-methyl-D-aspartate receptor channel probed by Mg2+ block

Yongling Zhu, Anthony Auerbach*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

The single-channel kinetics of extracellular Mg2+ block was used to probe K+ binding sites in the permeation pathway of rat recombinant NR1/NR2B NMDA receptor channels. K+ binds to three sites: two that are external and one that is internal to the site of Mg2+ block. The internal site is ∼0.84 through the electric field from the extracellular surface. The equilibrium dissociation constant for this site for K+ is 304 mM at 0 mV and with Mg2+ in the pore. The occupancy of any one of the three sites by K+ effectively prevents the association of extracellular Mg2+. Occupancy of the internal site also prevents Mg2+ permeation and increases (by approximately sevenfold) the rate constant for Mg2+ dissociation back to the extracellular solution. Under physiological intracellular ionic conditions and at -60 mV, there is ∼1,400-fold apparent decrease in the affinity of the channel for extracellular Mg2+ and ∼2-fold enhancement of the apparent voltage dependence of Mg2+ block caused by the voltage dependence of K+ occupancy of the external and internal sites.

Original languageEnglish (US)
Pages (from-to)287-297
Number of pages11
JournalJournal of General Physiology
Volume117
Issue number3
DOIs
StatePublished - 2001

Keywords

  • Channel block
  • Ion binding sites
  • Magnesium
  • Permeation
  • Selectivity

ASJC Scopus subject areas

  • Physiology

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