Biophys J, July 2000, p. 247-259, Vol. 79, No. 1

M2 Pore Mutations Convert the Glycine Receptor Channel from Being Anion- to Cation-Selective

Angelo Keramidas,^* Andrew J. Moorhouse,^* Chris R. French,^* Peter R. Schofield, and Peter H. Barry^*

 ^*School of Physiology and Pharmacology, University of New South Wales, Sydney 2052, and  The Garvan Institute for Medical Research, Darlinghurst, Sydney 2010, Australia

Three mutations in the M2 transmembrane domains of the chloride-conducting 1 homomeric glycine receptor (P250, 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 11 pS (outward current). The three inverse mutations, to those analyzed in this study, have previously been shown to make the 7 acetylcholine receptor channel anion-selective, indicating a common location for determinants of charge selectivity of inhibitory and excitatory ligand-gated ion channels.

Biophys J, July 2000, p. 247-259, Vol. 79, No. 1
© 2000 by the Biophysical Society   0006-3495/00/07/247/13  $2.00

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