Spermine and arcaine block and permeate N-methyl-D-aspartate receptor channels

Ricardo C. Araneda, Jian Yu Lan, Xin Zheng, R. Suzanne Zukin, Michael V.L. Bennett

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

Polyamines such as spermine are thought to be endogenous regulators of NMDA (N-methyl-D-aspartate)-type glutamate receptors. Polyamine block of NMDA receptors was studied in excised outside-out patches from rat hippocampal neurons and Xenopus oocytes expressing recombinant receptors. Extracellular spermine and arcaine reduced NMDA single-channel conductance in a voltage- dependent manner, with partial relief of block evident at large inside negative membrane potentials. Reducing extracellular Na+ concentration increased the apparent affinities for spermine and arcaine, indicating strong interaction between spermine and permeant ions. Internal spermine also blocked NMDA channels in a voltage-dependent manner, with relief of block evident at large inside positive potentials. The Woodhull model of channel block by an impermeant ion adequately described the actions of external spermine from -60 to +60 mV, but failed for more negative potentials. Eyring rate theory for a permeable blocker with two barriers and one binding site adequately described the voltage-dependent block and relief from block by both external and internal spermine over the range of -120 to +60 mV. These findings indicate that polyamines block and permeate neuronal NMDA receptor channels from the extracellular and intracellular sides, although sensitivity to internal spermine is probably too low to be physiologically relevant.

Original languageEnglish (US)
Pages (from-to)2899-2911
Number of pages13
JournalBiophysical journal
Volume76
Issue number6
DOIs
StatePublished - Jun 1999

    Fingerprint

ASJC Scopus subject areas

  • Biophysics

Cite this