title: A ring of eight conserved negatively charged amino acids doubles the conductance of BK channels and prevents inward rectification.
abstract: Large-conductance Ca2+-voltage-activated K+ channels (BK channels) control many key physiological processes, such as neurotransmitter release and muscle contraction. A signature feature of BK channels is that they have the largest single channel conductance of all K+ channels. Here we examine the mechanism of this large conductance. Comparison of the sequence of BK channels to lower-conductance K+ channels and to a crystallized bacterial K+ channel (MthK) revealed that BK channels have a ring of eight negatively charged glutamate residues at the entrance to the intracellular vestibule. This ring of charge, which is absent in lower-conductance K+ channels, is shown to double the conductance of BK channels for outward currents by increasing the concentration of K+ in the vestibule through an electrostatic mechanism. Removing the ring of charge converts BK channels to inwardly rectifying channels. Thus, a simple electrostatic mechanism contributes to the large conductance of BK channels.
authors.affiliation: Department of Physiology and Biophysics, University of Miami School of Medicine, 1600 N.W. 10th Avenue, Miami, FL 33136, USA.
authors.forename: Tinatin I
authors.initials: TI
authors.lastname: Brelidze
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Niu
authors.forename: Karl L
authors.initials: KL
authors.lastname: Magleby
mesh_terms: D000595:Amino Acid Sequence; D024342:Amino Acids, Acidic / Q000737:chemistry; D000818:Animals; D017124:Conserved Sequence; D004553:Electric Conductivity; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009865:Oocytes / Q000378:metabolism; D024681:Potassium Channels, Calcium-Activated / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D055672:Static Electricity; D014982:Xenopus laevis
chemical_list: D024342:Amino Acids, Acidic; D051036:Large-Conductance Calcium-Activated Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D011994:Recombinant Proteins