Charge scan reveals an extended region at the intracellular end of the GABA receptor pore that can influence ion selectivity

Virginia E. Wotring, David S. Weiss

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Selective permeability is a fundamental property of ion channels. The Cys-loop receptor superfamily is composed of both excitatory (ACh, 5-HT) and inhibitory (GABA, glycine) neurotransmitter-operated ion channels. In the GABA receptor, it has been previously shown that the charge selectivity of the integral pore can be altered by a single mutation near the intracellular end of the second transmembrane-spanning domain (TM2). We have extended these findings and now show that charge selectivity of the anionic ρ1 GABA receptor can be influenced by the introduction of glutamates, one at a time, over an 8-amino acid stretch (2′ to 5′) in the proposed intracellular end of TM2 and the TM1-TM2 intracellular linker. Depending on the position, glutamate substitutions in this region produced sodium to chloride permeability ratios (PNa+/Cl-) varying from 0.64 to 3.4 (wild type P Na+/Cl- = 0). In addition to providing insight into the mechanism of ion selectivity, this functional evidence supports a model proposed for the homologous nicotinic acetylcholine receptor in which regions of the protein, in addition to TM2, form the ion pathway.

Original languageEnglish (US)
Pages (from-to)87-97
Number of pages11
JournalJournal of General Physiology
Volume131
Issue number1
DOIs
StatePublished - Jan 2008

ASJC Scopus subject areas

  • Physiology

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