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Ion selectivity filter regulates local anesthetic inhibition of G-protein-gated inwardly rectifying K+ channels.
Slesinger PA
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The weaver mutation (G156S) in G-protein-gated inwardly rectifying K+ (GIRK) channels alters ion selectivity and reveals sensitivity to inhibition by a charged local anesthetic, QX-314, applied extracellularly. In this paper, disrupting the ion selectivity in another GIRK channel, chimera I1G1(M), generates a GIRK channel that is also inhibited by extracellular local anesthetics. I1G1(M) is a chimera of IRK1 (G-protein-insensitive) and GIRK1 and contains the hydrophobic domains (M1-pore-loop-M2) of GIRK1 (G1(M)) with the N- and C-terminal domains of IRK1 (I1). The local anesthetic binding site in I1G1(M) is indistinguishable from that in GIRK2(wv) channels. Whereas chimera I1G1(M) loses K+ selectivity, although there are no mutations in the pore-loop complex, chimera I1G2(M), which contains the hydrophobic domain from GIRK2, exhibits normal K+ selectivity. Mutation of two amino acids that are unique in the pore-loop complex of GIRK1 (F137S and A143T) restores K+ selectivity and eliminates the inhibition by extracellular local anesthetics, suggesting that the pore-loop complex prevents QX-314 from reaching the intrapore site. Alanine mutations in the extracellular half of the M2 transmembrane domain alter QX-314 inhibition, indicating the M2 forms part of the intrapore binding site. Finally, the inhibition of G-protein-activated currents by intracellular QX-314 appears to be different from that observed in nonselective GIRK channels. The results suggest that inward rectifiers contain an intrapore-binding site for local anesthetic that is normally inaccessible from extracellular charged local anesthetics.
Adams,
Tetraethylammonium block of the BNC1 channel.
1999, Pubmed,
Xenbase
Adams,
Tetraethylammonium block of the BNC1 channel.
1999,
Pubmed
,
Xenbase
Alreja,
QX-314 blocks the potassium but not the sodium-dependent component of the opiate response in locus coeruleus neurons.
1994,
Pubmed
Andrade,
Blockade of neurotransmitter-activated K+ conductance by QX-314 in the rat hippocampus.
1991,
Pubmed
Baukrowitz,
Use-dependent blockers and exit rate of the last ion from the multi-ion pore of a K+ channel.
1996,
Pubmed
Chan,
Control of channel activity through a unique amino acid residue of a G protein-gated inwardly rectifying K+ channel subunit.
1996,
Pubmed
,
Xenbase
Choe,
Three distinct structural environments of a transmembrane domain in the inwardly rectifying potassium channel ROMK1 defined by perturbation.
1995,
Pubmed
,
Xenbase
Collins,
Scanning mutagenesis of the putative transmembrane segments of Kir2.1, an inward rectifier potassium channel.
1997,
Pubmed
,
Xenbase
Doupnik,
The inward rectifier potassium channel family.
1995,
Pubmed
Doyle,
The structure of the potassium channel: molecular basis of K+ conduction and selectivity.
1998,
Pubmed
Duprat,
Heterologous multimeric assembly is essential for K+ channel activity of neuronal and cardiac G-protein-activated inward rectifiers.
1995,
Pubmed
,
Xenbase
Hedin,
Cloning of a Xenopus laevis inwardly rectifying K+ channel subunit that permits GIRK1 expression of IKACh currents in oocytes.
1996,
Pubmed
,
Xenbase
Heginbotham,
Mutations in the K+ channel signature sequence.
1994,
Pubmed
,
Xenbase
Huang,
Evidence that direct binding of G beta gamma to the GIRK1 G protein-gated inwardly rectifying K+ channel is important for channel activation.
1995,
Pubmed
,
Xenbase
Hurst,
External barium block of Shaker potassium channels: evidence for two binding sites.
1995,
Pubmed
,
Xenbase
Inanobe,
G beta gamma directly binds to the carboxyl terminus of the G protein-gated muscarinic K+ channel, GIRK1.
1995,
Pubmed
Kennedy,
Localization and interaction of epitope-tagged GIRK1 and CIR inward rectifier K+ channel subunits.
1996,
Pubmed
,
Xenbase
Kim,
Bcl-2 expression in neuroblastoma is differentially regulated by differentiation inducers.
1995,
Pubmed
Kofuji,
A unique P-region residue is required for slow voltage-dependent gating of a G protein-activated inward rectifier K+ channel expressed in Xenopus oocytes.
1996,
Pubmed
,
Xenbase
Kofuji,
Evidence that neuronal G-protein-gated inwardly rectifying K+ channels are activated by G beta gamma subunits and function as heteromultimers.
1995,
Pubmed
,
Xenbase
Kofuji,
Functional analysis of the weaver mutant GIRK2 K+ channel and rescue of weaver granule cells.
1996,
Pubmed
,
Xenbase
Krapivinsky,
The G-protein-gated atrial K+ channel IKACh is a heteromultimer of two inwardly rectifying K(+)-channel proteins.
1995,
Pubmed
,
Xenbase
Krapivinsky,
G beta gamma binds directly to the G protein-gated K+ channel, IKACh.
1995,
Pubmed
Kraus,
Molecular mechanism of diltiazem interaction with L-type Ca2+ channels.
1998,
Pubmed
,
Xenbase
Kubo,
Primary structure and functional expression of a rat G-protein-coupled muscarinic potassium channel.
1993,
Pubmed
,
Xenbase
Kunkel,
Identification of domains conferring G protein regulation on inward rectifier potassium channels.
1995,
Pubmed
,
Xenbase
Lambert,
Discrimination of post- and presynaptic GABAB receptor-mediated responses by tetrahydroaminoacridine in area CA3 of the rat hippocampus.
1993,
Pubmed
Lesage,
Molecular properties of neuronal G-protein-activated inwardly rectifying K+ channels.
1995,
Pubmed
,
Xenbase
Loussouarn,
Structure and dynamics of the pore of inwardly rectifying K(ATP) channels.
2000,
Pubmed
Lu,
Architecture of a K+ channel inner pore revealed by stoichiometric covalent modification.
1999,
Pubmed
,
Xenbase
Lu,
Electrostatic tuning of Mg2+ affinity in an inward-rectifier K+ channel.
1994,
Pubmed
,
Xenbase
Minor,
Transmembrane structure of an inwardly rectifying potassium channel.
1999,
Pubmed
Nathan,
The slow inhibitory postsynaptic potential in rat hippocampal CA1 neurones is blocked by intracellular injection of QX-314.
1990,
Pubmed
Nicoll,
Functional comparison of neurotransmitter receptor subtypes in mammalian central nervous system.
1990,
Pubmed
North,
Twelfth Gaddum memorial lecture. Drug receptors and the inhibition of nerve cells.
1989,
Pubmed
Otis,
Characterization of synaptically elicited GABAB responses using patch-clamp recordings in rat hippocampal slices.
1993,
Pubmed
Patil,
A potassium channel mutation in weaver mice implicates membrane excitability in granule cell differentiation.
1995,
Pubmed
Philipson,
Functional expression of an epitope-tagged G protein-coupled K+ channel (GIRK1).
1995,
Pubmed
Ragsdale,
Common molecular determinants of local anesthetic, antiarrhythmic, and anticonvulsant block of voltage-gated Na+ channels.
1996,
Pubmed
Reuveny,
Activation of the cloned muscarinic potassium channel by G protein beta gamma subunits.
1994,
Pubmed
,
Xenbase
Reuveny,
Contributions of a negatively charged residue in the hydrophobic domain of the IRK1 inwardly rectifying K+ channel to K(+)-selective permeation.
1996,
Pubmed
,
Xenbase
Signorini,
Normal cerebellar development but susceptibility to seizures in mice lacking G protein-coupled, inwardly rectifying K+ channel GIRK2.
1997,
Pubmed
Silverman,
A regenerative link in the ionic fluxes through the weaver potassium channel underlies the pathophysiology of the mutation.
1996,
Pubmed
,
Xenbase
Silverman,
Asymmetrical contributions of subunit pore regions to ion selectivity in an inward rectifier K+ channel.
1998,
Pubmed
,
Xenbase
Slesinger,
Defective gamma-aminobutyric acid type B receptor-activated inwardly rectifying K+ currents in cerebellar granule cells isolated from weaver and Girk2 null mutant mice.
1997,
Pubmed
,
Xenbase
Slesinger,
Functional effects of the mouse weaver mutation on G protein-gated inwardly rectifying K+ channels.
1996,
Pubmed
,
Xenbase
Slesinger,
Identification of structural elements involved in G protein gating of the GIRK1 potassium channel.
1995,
Pubmed
,
Xenbase
Sunami,
Sodium channel selectivity filter regulates antiarrhythmic drug binding.
1997,
Pubmed
,
Xenbase
TRAUTWEIN,
[Mechanism of membrane effect of acetylcholine on myocardial fibers].
1958,
Pubmed
Tucker,
Heteromeric channel formation and Ca(2+)-free media reduce the toxic effect of the weaver Kir 3.2 allele.
1996,
Pubmed
,
Xenbase
Velimirovic,
The K+ channel inward rectifier subunits form a channel similar to neuronal G protein-gated K+ channel.
1996,
Pubmed
,
Xenbase
Woodhull,
Ionic blockage of sodium channels in nerve.
1973,
Pubmed
Yamada,
Different subtypes of GABAB receptors are present at pre- and postsynaptic sites within the rat dorsolateral septal nucleus.
1999,
Pubmed
Yellen,
Mutations affecting internal TEA blockade identify the probable pore-forming region of a K+ channel.
1991,
Pubmed
