Intracellular β-Nicotinamide Adenine Dinucleotide Inhibits the Skeletal Muscle ClC-1 Chloride Channel*

التفاصيل البيبلوغرافية
العنوان: Intracellular β-Nicotinamide Adenine Dinucleotide Inhibits the Skeletal Muscle ClC-1 Chloride Channel*
المؤلفون: Brett Bennetts, Michael W. Parker, Yawei Yu, Tsung-Yu Chen
بيانات النشر: American Society for Biochemistry and Molecular Biology, 2012.
سنة النشر: 2012
مصطلحات موضوعية: Intracellular Fluid, Models, Molecular, Patch-Clamp Techniques, Intracellular pH, Xenopus, Molecular Sequence Data, Nicotinamide adenine dinucleotide, Biology, Biochemistry, Cofactor, Cell Line, Membrane Potentials, chemistry.chemical_compound, Adenosine Triphosphate, Chloride Channels, Membrane Biology, Animals, Humans, Computer Simulation, Amino Acid Sequence, Muscle, Skeletal, Molecular Biology, Binding Sites, Nicotinamide, urogenital system, Cell Biology, Hydrogen-Ion Concentration, NAD, Protein Structure, Tertiary, Kinetics, chemistry, Amino Acid Substitution, Chloride channel, Biophysics, biology.protein, Mutagenesis, Site-Directed, Oocytes, NAD+ kinase, Adenosine triphosphate, Intracellular, Protein Binding
الوصف: ClC-1 is the dominant sarcolemmal chloride channel and plays an important role in regulating membrane excitability that is underscored by ClC-1 mutations in congenital myotonia. Here we show that the coenzyme β-nicotinamide adenine dinucleotide (NAD), an important metabolic regulator, robustly inhibits ClC-1 when included in the pipette solution in whole cell patch clamp experiments and when transiently applied to inside-out patches. The oxidized (NAD(+)) form of the coenzyme was more efficacious than the reduced (NADH) form, and inhibition by both was greatly enhanced by acidification. Molecular modeling, based on the structural coordinates of the homologous ClC-5 and CmClC proteins and in silico docking, suggest that NAD(+) binds with the adenine base deep in a cleft formed by ClC-1 intracellular cystathionine β-synthase domains, and the nicotinamide base interacts with the membrane-embedded channel domain. Consistent with predictions from the models, mutation of residues in cystathionine β-synthase and channel domains either attenuated (G200R, T636A, H847A) or abrogated (L848A) the effect of NAD(+). In addition, the myotonic mutations G200R and Y261C abolished potentiation of NAD(+) inhibition at low pH. Our results identify a new biological role for NAD and suggest that the main physiological relevance may be the exquisite sensitivity to intracellular pH that NAD(+) inhibition imparts to ClC-1 gating. These findings are consistent with the reduction of sarcolemmal chloride conductance that occurs upon acidification of skeletal muscle and suggest a previously unexplored mechanism in the pathophysiology of myotonia.
اللغة: English
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::01c156f0b50e43d57351ff3c74948d3fTest
https://europepmc.org/articles/PMC3406667Test/
حقوق: OPEN
رقم الانضمام: edsair.doi.dedup.....01c156f0b50e43d57351ff3c74948d3f
قاعدة البيانات: OpenAIRE
ResultId 1
Header edsair
OpenAIRE
edsair.doi.dedup.....01c156f0b50e43d57351ff3c74948d3f
771
3

unknown
771.052124023438
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&scope=site&db=edsair&AN=edsair.doi.dedup.....01c156f0b50e43d57351ff3c74948d3f&custid=s6537998&authtype=sso
FullText Array ( [Availability] => 0 )
Items Array ( [Name] => Title [Label] => Title [Group] => Ti [Data] => Intracellular β-Nicotinamide Adenine Dinucleotide Inhibits the Skeletal Muscle ClC-1 Chloride Channel* )
Array ( [Name] => Author [Label] => Authors [Group] => Au [Data] => <searchLink fieldCode="AR" term="%22Brett+Bennetts%22">Brett Bennetts</searchLink><br /><searchLink fieldCode="AR" term="%22Michael+W%2E+Parker%22">Michael W. Parker</searchLink><br /><searchLink fieldCode="AR" term="%22Yawei+Yu%22">Yawei Yu</searchLink><br /><searchLink fieldCode="AR" term="%22Tsung-Yu+Chen%22">Tsung-Yu Chen</searchLink> )
Array ( [Name] => Publisher [Label] => Publisher Information [Group] => PubInfo [Data] => American Society for Biochemistry and Molecular Biology, 2012. )
Array ( [Name] => DatePubCY [Label] => Publication Year [Group] => Date [Data] => 2012 )
Array ( [Name] => Subject [Label] => Subject Terms [Group] => Su [Data] => <searchLink fieldCode="DE" term="%22Intracellular+Fluid%22">Intracellular Fluid</searchLink><br /><searchLink fieldCode="DE" term="%22Models%2C+Molecular%22">Models, Molecular</searchLink><br /><searchLink fieldCode="DE" term="%22Patch-Clamp+Techniques%22">Patch-Clamp Techniques</searchLink><br /><searchLink fieldCode="DE" term="%22Intracellular+pH%22">Intracellular pH</searchLink><br /><searchLink fieldCode="DE" term="%22Xenopus%22">Xenopus</searchLink><br /><searchLink fieldCode="DE" term="%22Molecular+Sequence+Data%22">Molecular Sequence Data</searchLink><br /><searchLink fieldCode="DE" term="%22Nicotinamide+adenine+dinucleotide%22">Nicotinamide adenine dinucleotide</searchLink><br /><searchLink fieldCode="DE" term="%22Biology%22">Biology</searchLink><br /><searchLink fieldCode="DE" term="%22Biochemistry%22">Biochemistry</searchLink><br /><searchLink fieldCode="DE" term="%22Cofactor%22">Cofactor</searchLink><br /><searchLink fieldCode="DE" term="%22Cell+Line%22">Cell Line</searchLink><br /><searchLink fieldCode="DE" term="%22Membrane+Potentials%22">Membrane Potentials</searchLink><br /><searchLink fieldCode="DE" term="%22chemistry%2Echemical%5Fcompound%22">chemistry.chemical_compound</searchLink><br /><searchLink fieldCode="DE" term="%22Adenosine+Triphosphate%22">Adenosine Triphosphate</searchLink><br /><searchLink fieldCode="DE" term="%22Chloride+Channels%22">Chloride Channels</searchLink><br /><searchLink fieldCode="DE" term="%22Membrane+Biology%22">Membrane Biology</searchLink><br /><searchLink fieldCode="DE" term="%22Animals%22">Animals</searchLink><br /><searchLink fieldCode="DE" term="%22Humans%22">Humans</searchLink><br /><searchLink fieldCode="DE" term="%22Computer+Simulation%22">Computer Simulation</searchLink><br /><searchLink fieldCode="DE" term="%22Amino+Acid+Sequence%22">Amino Acid Sequence</searchLink><br /><searchLink fieldCode="DE" term="%22Muscle%2C+Skeletal%22">Muscle, Skeletal</searchLink><br /><searchLink fieldCode="DE" term="%22Molecular+Biology%22">Molecular Biology</searchLink><br /><searchLink fieldCode="DE" term="%22Binding+Sites%22">Binding Sites</searchLink><br /><searchLink fieldCode="DE" term="%22Nicotinamide%22">Nicotinamide</searchLink><br /><searchLink fieldCode="DE" term="%22urogenital+system%22">urogenital system</searchLink><br /><searchLink fieldCode="DE" term="%22Cell+Biology%22">Cell Biology</searchLink><br /><searchLink fieldCode="DE" term="%22Hydrogen-Ion+Concentration%22">Hydrogen-Ion Concentration</searchLink><br /><searchLink fieldCode="DE" term="%22NAD%22">NAD</searchLink><br /><searchLink fieldCode="DE" term="%22Protein+Structure%2C+Tertiary%22">Protein Structure, Tertiary</searchLink><br /><searchLink fieldCode="DE" term="%22Kinetics%22">Kinetics</searchLink><br /><searchLink fieldCode="DE" term="%22chemistry%22">chemistry</searchLink><br /><searchLink fieldCode="DE" term="%22Amino+Acid+Substitution%22">Amino Acid Substitution</searchLink><br /><searchLink fieldCode="DE" term="%22Chloride+channel%22">Chloride channel</searchLink><br /><searchLink fieldCode="DE" term="%22Biophysics%22">Biophysics</searchLink><br /><searchLink fieldCode="DE" term="%22biology%2Eprotein%22">biology.protein</searchLink><br /><searchLink fieldCode="DE" term="%22Mutagenesis%2C+Site-Directed%22">Mutagenesis, Site-Directed</searchLink><br /><searchLink fieldCode="DE" term="%22Oocytes%22">Oocytes</searchLink><br /><searchLink fieldCode="DE" term="%22NAD%2B+kinase%22">NAD+ kinase</searchLink><br /><searchLink fieldCode="DE" term="%22Adenosine+triphosphate%22">Adenosine triphosphate</searchLink><br /><searchLink fieldCode="DE" term="%22Intracellular%22">Intracellular</searchLink><br /><searchLink fieldCode="DE" term="%22Protein+Binding%22">Protein Binding</searchLink> )
Array ( [Name] => Abstract [Label] => Description [Group] => Ab [Data] => ClC-1 is the dominant sarcolemmal chloride channel and plays an important role in regulating membrane excitability that is underscored by ClC-1 mutations in congenital myotonia. Here we show that the coenzyme β-nicotinamide adenine dinucleotide (NAD), an important metabolic regulator, robustly inhibits ClC-1 when included in the pipette solution in whole cell patch clamp experiments and when transiently applied to inside-out patches. The oxidized (NAD(+)) form of the coenzyme was more efficacious than the reduced (NADH) form, and inhibition by both was greatly enhanced by acidification. Molecular modeling, based on the structural coordinates of the homologous ClC-5 and CmClC proteins and in silico docking, suggest that NAD(+) binds with the adenine base deep in a cleft formed by ClC-1 intracellular cystathionine β-synthase domains, and the nicotinamide base interacts with the membrane-embedded channel domain. Consistent with predictions from the models, mutation of residues in cystathionine β-synthase and channel domains either attenuated (G200R, T636A, H847A) or abrogated (L848A) the effect of NAD(+). In addition, the myotonic mutations G200R and Y261C abolished potentiation of NAD(+) inhibition at low pH. Our results identify a new biological role for NAD and suggest that the main physiological relevance may be the exquisite sensitivity to intracellular pH that NAD(+) inhibition imparts to ClC-1 gating. These findings are consistent with the reduction of sarcolemmal chloride conductance that occurs upon acidification of skeletal muscle and suggest a previously unexplored mechanism in the pathophysiology of myotonia. )
Array ( [Name] => Language [Label] => Language [Group] => Lang [Data] => English )
Array ( [Name] => URL [Label] => Access URL [Group] => URL [Data] => <link linkTarget="URL" linkTerm="https://explore.openaire.eu/search/publication?articleId=doi_dedup___::01c156f0b50e43d57351ff3c74948d3f" linkWindow="_blank">https://explore.openaire.eu/search/publication?articleId=doi_dedup___::01c156f0b50e43d57351ff3c74948d3f</link><br /><link linkTarget="URL" linkTerm="https://europepmc.org/articles/PMC3406667/" linkWindow="_blank">https://europepmc.org/articles/PMC3406667/</link> )
Array ( [Name] => Copyright [Label] => Rights [Group] => Cpyrght [Data] => OPEN )
Array ( [Name] => AN [Label] => Accession Number [Group] => ID [Data] => edsair.doi.dedup.....01c156f0b50e43d57351ff3c74948d3f )
RecordInfo Array ( [BibEntity] => Array ( [Languages] => Array ( [0] => Array ( [Text] => English ) ) [Subjects] => Array ( [0] => Array ( [SubjectFull] => Intracellular Fluid [Type] => general ) [1] => Array ( [SubjectFull] => Models, Molecular [Type] => general ) [2] => Array ( [SubjectFull] => Patch-Clamp Techniques [Type] => general ) [3] => Array ( [SubjectFull] => Intracellular pH [Type] => general ) [4] => Array ( [SubjectFull] => Xenopus [Type] => general ) [5] => Array ( [SubjectFull] => Molecular Sequence Data [Type] => general ) [6] => Array ( [SubjectFull] => Nicotinamide adenine dinucleotide [Type] => general ) [7] => Array ( [SubjectFull] => Biology [Type] => general ) [8] => Array ( [SubjectFull] => Biochemistry [Type] => general ) [9] => Array ( [SubjectFull] => Cofactor [Type] => general ) [10] => Array ( [SubjectFull] => Cell Line [Type] => general ) [11] => Array ( [SubjectFull] => Membrane Potentials [Type] => general ) [12] => Array ( [SubjectFull] => chemistry.chemical_compound [Type] => general ) [13] => Array ( [SubjectFull] => Adenosine Triphosphate [Type] => general ) [14] => Array ( [SubjectFull] => Chloride Channels [Type] => general ) [15] => Array ( [SubjectFull] => Membrane Biology [Type] => general ) [16] => Array ( [SubjectFull] => Animals [Type] => general ) [17] => Array ( [SubjectFull] => Humans [Type] => general ) [18] => Array ( [SubjectFull] => Computer Simulation [Type] => general ) [19] => Array ( [SubjectFull] => Amino Acid Sequence [Type] => general ) [20] => Array ( [SubjectFull] => Muscle, Skeletal [Type] => general ) [21] => Array ( [SubjectFull] => Molecular Biology [Type] => general ) [22] => Array ( [SubjectFull] => Binding Sites [Type] => general ) [23] => Array ( [SubjectFull] => Nicotinamide [Type] => general ) [24] => Array ( [SubjectFull] => urogenital system [Type] => general ) [25] => Array ( [SubjectFull] => Cell Biology [Type] => general ) [26] => Array ( [SubjectFull] => Hydrogen-Ion Concentration [Type] => general ) [27] => Array ( [SubjectFull] => NAD [Type] => general ) [28] => Array ( [SubjectFull] => Protein Structure, Tertiary [Type] => general ) [29] => Array ( [SubjectFull] => Kinetics [Type] => general ) [30] => Array ( [SubjectFull] => chemistry [Type] => general ) [31] => Array ( [SubjectFull] => Amino Acid Substitution [Type] => general ) [32] => Array ( [SubjectFull] => Chloride channel [Type] => general ) [33] => Array ( [SubjectFull] => Biophysics [Type] => general ) [34] => Array ( [SubjectFull] => biology.protein [Type] => general ) [35] => Array ( [SubjectFull] => Mutagenesis, Site-Directed [Type] => general ) [36] => Array ( [SubjectFull] => Oocytes [Type] => general ) [37] => Array ( [SubjectFull] => NAD+ kinase [Type] => general ) [38] => Array ( [SubjectFull] => Adenosine triphosphate [Type] => general ) [39] => Array ( [SubjectFull] => Intracellular [Type] => general ) [40] => Array ( [SubjectFull] => Protein Binding [Type] => general ) ) [Titles] => Array ( [0] => Array ( [TitleFull] => Intracellular β-Nicotinamide Adenine Dinucleotide Inhibits the Skeletal Muscle ClC-1 Chloride Channel* [Type] => main ) ) ) [BibRelationships] => Array ( [HasContributorRelationships] => Array ( [0] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Brett Bennetts ) ) ) [1] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Michael W. Parker ) ) ) [2] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Yawei Yu ) ) ) [3] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Tsung-Yu Chen ) ) ) ) [IsPartOfRelationships] => Array ( [0] => Array ( [BibEntity] => Array ( [Dates] => Array ( [0] => Array ( [D] => 11 [M] => 06 [Type] => published [Y] => 2012 ) ) [Identifiers] => Array ( [0] => Array ( [Type] => issn-locals [Value] => edsair ) [1] => Array ( [Type] => issn-locals [Value] => edsairFT ) ) ) ) ) ) )
IllustrationInfo