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

Three mutations in the M2 transmembrane domains of the chloride-conducting alpha 1 homomeric glycine receptor (P250 Delta, A251E, and T265V), which normally mediate fast inhibitory neurotransmission, produced a cation-selective channel with P-Cl/P-Na, = 0.27 (wild-type P-Cl/P-Na = 25), a permeability sequence P-Cs > P-K > P-Na > P-Li, an impermeability to Ca2+ and a reduced glycine sensitivity. Outside-out patch measurements indicated reversed and accentuated rectification with extremely low mean single channel conductances of 3 pS (inward current) and II pS (outward current). The three inverse mutations, to those analyzed in this study, have previously been shown to make the alpha 7 acetylcholine receptor channel anion-selective, indicating a common location for determinants of charge selectivity of inhibitory and excitatory ligand-gated ion channels.