The contribution of proline 250 (P-2′) to pore diameter and ion selectivity in the human glycine receptor channel

The glycine receptor-channel (GlyR) mediates neuronal inhibition by selectively allowing the passage of Cl- ions through its channel. The pore region for ion selectivity is localised to the constricted internal end of the M2 transmembrane domain. This paper investigates the contribution of the P-2' residue in determining pore diameter and ion charge selectivity of the GlyR. The deletion of this proline has been shown to decrease the anion/cation permeability ratio, with P-Cl/P-Na decreasing from similar to27 to similar to4. We show that the P-2', deletion by itself produces a GlyR with a larger pore diameter (similar to0.69 nm) than the wild type value (similar to0.54 nm). This confirms that the P-2' residue reduces pore size, which suggests that, in addition to electrostatic effects, pore size also contributes to ion-charge selectivity. (C) 2003 Elsevier Ireland Ltd. All rights reserved.