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.