title: Charge scan reveals an extended region at the intracellular end of the GABA receptor pore that can influence ion selectivity.
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 rho1 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 (P(Na)+(/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.
authors: Department of Neurobiology, University of Alabama at Birmingham, AL 35294, USA.
authors: Virginia E
authors: VE
authors: Wotring
authors: David S
authors: DS
authors: Weiss
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002462:Cell Membrane / Q000502:physiology; D002463:Cell Membrane Permeability / Q000502:physiology*; D004594:Electrophysiology; D005260:Female; D018698:Glutamic Acid / Q000032:analysis; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology*; D008954:Models, Biological; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009865:Oocytes / Q000502:physiology; D018408:Patch-Clamp Techniques; D018080:Receptors, GABA-B / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D014982:Xenopus laevis
chemical_list: D018080:Receptors, GABA-B; D018698:Glutamic Acid