title: Functional interactions between K+ pore residues located in different subunits.
abstract: The aqueous pore (P-region) of homotetrameric voltage-gated K+ channels has been modeled as a radially symmetrical eight-stranded antiparallel beta-barrel to which each of the four subunits contributes equally. This model has hydrogen bonding between residues located on adjacent subunits and predicts that subunit interactions might have functional consequences. Previously we have used point mutations and an electrophysiological assay to detect functional interactions between a pair of residues at positions 369 and 374 in the P-region, but we could not distinguish between intra- and intersubunit interactions. In the present paper, we present evidence for interaction across subunit boundaries after co-injecting two cRNAs encoding subunits differing from each other at either position 369 or 374. Comparison of the phenotypes of homo- and heterotetrameric channels suggests that pore residues residing in adjacent subunits form a closely packed structure which determines both ion conductance and stability of the open state of the channel. Our results are consistent with a structure in which pore residues 369 and 374 are located in close proximity on adjacent antiparallel strands to allow both intra- and intersubunit interactions.
authors.affiliation: Department of Anesthesiology, Baylor College of Medicine, Houston, Texas 77030.
authors.forename: G E
authors.initials: GE
authors.lastname: Kirsch
authors.forename: J A
authors.initials: JA
authors.lastname: Drewe
authors.forename: M
authors.initials: M
authors.lastname: De Biasi
authors.forename: H A
authors.initials: HA
authors.lastname: Hartmann
authors.forename: A M
authors.initials: AM
authors.lastname: Brown
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D004274:DNA, Recombinant / Q000378:metabolism; D004553:Electric Conductivity; D004926:Escherichia coli / Q000235:genetics; D005260:Female; D046911:Macromolecular Substances; D008564:Membrane Potentials / Q000187:drug effects; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009865:Oocytes / Q000187:drug effects / Q000502:physiology; D017354:Point Mutation; D015221:Potassium Channels / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins / Q000187:drug effects / Q000378:metabolism; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D014158:Transcription, Genetic
chemical_list: D004274:DNA, Recombinant; D046911:Macromolecular Substances; D015221:Potassium Channels; D011994:Recombinant Proteins; D013757:Tetraethylammonium Compounds; D019789:Tetraethylammonium