Journal ArticleDOI
Gating of inwardly rectifying K+ channels localized to a single negatively charged residue
TLDR
A single amino-acid change within the putative transmembrane domain M2, aspartate in IRK1 to the corresponding asparagine in ROMK1, controls the gating phenotype, and seems to be a crucial determinant of gating.Abstract:
Inwardly rectifying K+ channels (IRKs) conduct current preferentially in the inward direction. This inward rectification has two components: voltage-dependent blockade by intracellular Mg2+ (Mg2+i) and intrinsic gating. Two members of this channel family, IRK1 (ref. 10) and ROMK1 (ref. 11), differ markedly in affinity for Mg2+i (ref. 12). We found that IRK1 and ROMK1 differ in voltage-dependent gating and searched for the gating structure by large-scale and site-directed mutagenesis. We found that a single amino-acid change within the putative transmembrane domain M2, aspartate (D) in IRK1 to the corresponding asparagine (N) in ROMK1, controls the gating phenotype. Mutation D172N in IRK1 produced ROMK1-like gating whereas the reverse mutation in ROMK1--N171D--produced IRK1-like gating. Thus, a single negatively charged residue seems to be a crucial determinant of gating.read more
Citations
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Journal ArticleDOI
Reconstitution of IKATP: an inward rectifier subunit plus the sulfonylurea receptor.
Nobuya Inagaki,Tohru Gonoi,John P. Clement,Noriyuki Namba,Johji Inazawa,Gabriela Gonzalez,Lydia Aguilar-Bryan,Susumu Seino,Joseph Bryan +8 more
TL;DR: Gene mapping data indicate that these pancreatic β cell potassium channels are a complex composed of at least two subunits-BIR, a member of the inward rectifier potassium channel family, and SUR, a members of the ATP-binding cassette superfamily.
Journal ArticleDOI
Inwardly Rectifying Potassium Channels: Their Structure, Function, and Physiological Roles
Hiroshi Hibino,Atsushi Inanobe,Kazuharu Furutani,Shingo Murakami,Ian Findlay,Yoshihisa Kurachi +5 more
TL;DR: The crystal structure of different Kir channels is opening the way to understanding the structure-function relationships of this simple but diverse ion channel family.
Journal ArticleDOI
Potassium channel block by cytoplasmic polyamines as the mechanism of intrinsic rectification
TL;DR: The results suggest that intrinsic rectification results from voltage-dependent block of the channel pore by polyamines, not from a voltage sensor intrinsic to the channel protein.
Journal ArticleDOI
Crystal Structure of the Potassium Channel KirBac1.1 in the Closed State
Anling Kuo,Jacqueline M. Gulbis,Jennifer F. Antcliff,Tahmina Rahman,Edward D. Lowe,Jochen Zimmer,Jonathan Cuthbertson,Frances M. Ashcroft,Takayuki Ezaki,Declan A. Doyle +9 more
TL;DR: The structure of the entire prokaryotic Kir channel assembly, in the closed state, refined to a resolution of 3.65 angstroms, suggests that gating involves coupling between the intracellular and membrane domains and suggests that initiation of gating by membrane or intrACEllular signals represents different entry points to a common mechanistic pathway.
Journal ArticleDOI
Inward rectifier potassium channels
TL;DR: In the past three years, remarkable progress in research on the molecular basis of inward rectification has been made, with significant implications for basic understanding and pharmacological manipulation of cellular excitability as discussed by the authors.
References
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Journal ArticleDOI
Site-directed mutagenesis by overlap extension using the polymerase chain reaction.
TL;DR: In this paper, complementary oligodeoxyribonucleotide (oligo) primers and the polymerase chain reaction are used to generate two DNA fragments having overlapping ends, and these fragments are combined in a subsequent 'fusion' reaction in which the overlapping ends anneal, allowing the 3' overlap of each strand to serve as a primer for the three' extension of the complementary strand.
Book
Ionic channels of excitable membranes
TL;DR: The Ionic Channel of Excitable Membranes (ICOMB) as discussed by the authors is an extended version of ICOMB with new chapters on fast chemical synapses, modulation through G protein coupled receptors and second messenger systems, molecules cloning, site directed mutagenesis, and cell biology.
Journal ArticleDOI
Ionic Blockage of Sodium Channels in Nerve
TL;DR: A voltage-dependent block of sodium channels by hydrogen ions is explained, which shifts the responses of sodium channel "gates" to voltage, probably by altering the surface potential of the nerve.
Journal ArticleDOI
Primary structure and functional expression of a mouse inward rectifier potassium channel
TL;DR: The IRK1 channel and an ATP-regulated K+ channel show extensive sequence similarity and constitute a new superfamily, similar to the inner core structure of voltage-gated K+ channels.
Journal ArticleDOI
Cloning and expression of an inwardly rectifying ATP-regulated potassium channel
Kevin Ho,Colin G. Nichols,W. J. Lederer,Jonathan Lytton,Peter M. Vassilev,M V Kanazirska,S.C. Hebert +6 more
TL;DR: A complementary DNA encoding an ATP-regulated potassium channel has been isolated by expression cloning from rat kidney and the presence of an H5 region, which is likely to form the ion conduction pathway, indicates that the protein may share a common origin with voltage-gated potassium channel proteins.