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

Neurosci Lett. 2003 Nov 20;351(3):196-200. doi: 10.1016/j.neulet.2003.08.005.

Abstract

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 approximately 27 to approximately 4. We show that the P-2' deletion by itself produces a GlyR with a larger pore diameter ( approximately 0.69 nm) than the wild type value ( approximately 0.54 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Humans
  • Ion Channel Gating* / genetics
  • Molecular Sequence Data
  • Mutation
  • Proline / chemistry*
  • Proline / genetics
  • Proline / physiology*
  • Receptors, Glycine / chemistry*
  • Receptors, Glycine / genetics
  • Receptors, Glycine / physiology*

Substances

  • Receptors, Glycine
  • Proline