Charge selectivity of the Cys‐loop family of ligand‐gated ion channels

• Published in: Journal of neurochemistry 2005-01, Vol.92 (2), p.217-225
• Main Authors: Jensen, Marianne L., Schousboe, Arne, Ahring, Philip K.
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Cell membranes. Ionic channels. Membrane pores; Cell structures and functions; channel; Cys‐loop; Fundamental and applied biological sciences. Psychology; Humans; Ion Channel Gating - physiology; Ion Channels - metabolism; ions; ligand; Ligands; Molecular and cellular biology; Molecular Sequence Data; Protein Structure, Tertiary - physiology; selectivity; Sequence Homology, Amino Acid
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2004.02883.x

The determinants of charge selectivity of the Cys‐loop family of ligand‐gated ion channels have been studied for more than a decade. The investigations have mainly covered homomeric receptors e.g. the nicotinic acetylcholine receptor α7, the glycine receptor α1 and the serotonin receptor 5‐HT3A. Only recently, the determinants of charge selectivity of heteromeric receptors have been addressed for the GABAA receptor α2β3γ2. For all receptor subtypes, the selectivity determinants have been located to an intracellular linker between transmembrane domains M1 and M2. Two features of the M1–M2 linker appear to control ion selectivity. A central role for charged amino acid residues in selectivity has been almost universally observed. Furthermore, recent studies point to an important role of the size of the narrowest constriction in the pore. In the present review, these determinants of charge selectivity of the Cys‐loop family of ligand‐gated ion channels will be discussed in detail.