M2 pore mutations convert the glycine receptor channel from being anion- to cation-selective

Citation
A. Keramidas et al., M2 pore mutations convert the glycine receptor channel from being anion- to cation-selective, BIOPHYS J, 79(1), 2000, pp. 247-259
Citations number
43
Categorie Soggetti
Biochemistry & Biophysics
Journal title
BIOPHYSICAL JOURNAL
ISSN journal
00063495 → ACNP
Volume
79
Issue
1
Year of publication
2000
Pages
247 - 259
Database
ISI
SICI code
0006-3495(200007)79:1<247:MPMCTG>2.0.ZU;2-S
Abstract
Three mutations in the M2 transmembrane domains of the chloride-conducting alpha 1 homomeric glycine receptor (P250 Delta, A251E, and T265V), which no rmally mediate fast inhibitory neurotransmission, produced a cation-selecti ve channel with P-Cl/P-Na, = 0.27 (wild-type P-Cl/P-Na = 25), a permeabilit y sequence P-Cs > P-K > P-Na > P-Li, an impermeability to Ca2+ and a reduce d glycine sensitivity. Outside-out patch measurements indicated reversed an d accentuated rectification with extremely low mean single channel conducta nces of 3 pS (inward current) and II pS (outward current). The three invers e mutations, to those analyzed in this study, have previously been shown to make the alpha 7 acetylcholine receptor channel anion-selective, indicatin g a common location for determinants of charge selectivity of inhibitory an d excitatory ligand-gated ion channels.