Three mutations in the M2 transmembrane domains of the chloride- conducting α1 homomeric glycine receptor (P250Δ, 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 Ca 2+ , 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 11 pS (outward current). The three inverse mutations, to those analyzed in this study, have previously been shown to make the α7 acetylcholine receptor channel anion- selective, indicating a common location for determinants of charge selectivity of inhibitory and excitatory ligand-gated ion channels.
Keramidas, A., Moorhouse, A. J., French, C. R., Schofield, P. R., & Barry, P. H. (2000). M2 pore mutations convert the glycine receptor channel from being anion- to cation-selective. Biophysical Journal, 79(1), 247–259. https://doi.org/10.1016/S0006-3495(00)76287-4