Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
J Biol Chem
2013 Feb 15;2887:4782-91. doi: 10.1074/jbc.M112.434266.
Show Gene links
Show Anatomy links
Proton sensors in the pore domain of the cardiac voltage-gated sodium channel.
Jones DK
,
Peters CH
,
Allard CR
,
Claydon TW
,
Ruben PC
.
???displayArticle.abstract???
Protons impart isoform-specific modulation of inactivation in neuronal, skeletal muscle, and cardiac voltage-gated sodium (Na(V)) channels. Although the structural basis of proton block in Na(V) channels has been well described, the amino acid residues responsible for the changes in Na(V) kinetics during extracellular acidosis are as yet unknown. We expressed wild-type (WT) and two pore mutant constructs (H880Q and C373F) of the human cardiac Na(V) channel, Na(V)1.5, in Xenopus oocytes. C373F and H880Q both attenuated proton block, abolished proton modulation of use-dependent inactivation, and altered pH modulation of the steady-state and kinetic parameters of slow inactivation. Additionally, C373F significantly reduced the maximum probability of use-dependent inactivation and slow inactivation, relative to WT. H880Q also significantly reduced the maximum probability of slow inactivation and shifted the voltage dependence of activation and fast inactivation to more positive potentials, relative to WT. These data suggest that Cys-373 and His-880 in Na(V)1.5 are proton sensors for use-dependent and slow inactivation and have implications in isoform-specific modulation of Na(V) channels.
Antzelevitch,
Electrophysiological effects of ranolazine, a novel antianginal agent with antiarrhythmic properties.
2004, Pubmed
Antzelevitch,
Electrophysiological effects of ranolazine, a novel antianginal agent with antiarrhythmic properties.
2004,
Pubmed
Balser,
External pore residue mediates slow inactivation in mu 1 rat skeletal muscle sodium channels.
1996,
Pubmed
,
Xenbase
Bazett,
The time relations of the blood-pressure changes after excision of the adrenal glands, with some observations on blood volume changes.
1920,
Pubmed
Bendahhou,
Impairment of slow inactivation as a common mechanism for periodic paralysis in DIIS4-S5.
2002,
Pubmed
Bendahhou,
Activation and inactivation of the voltage-gated sodium channel: role of segment S5 revealed by a novel hyperkalaemic periodic paralysis mutation.
1999,
Pubmed
Capes,
Gating transitions in the selectivity filter region of a sodium channel are coupled to the domain IV voltage sensor.
2012,
Pubmed
Chen,
Neuromodulation of Na+ channel slow inactivation via cAMP-dependent protein kinase and protein kinase C.
2006,
Pubmed
Claydon,
Two pore residues mediate acidosis-induced enhancement of C-type inactivation of the Kv1.4 K(+) channel.
2002,
Pubmed
,
Xenbase
Claydon,
Inhibition of the K+ channel kv1.4 by acidosis: protonation of an extracellular histidine slows the recovery from N-type inactivation.
2000,
Pubmed
,
Xenbase
Cuello,
Structural mechanism of C-type inactivation in K(+) channels.
2010,
Pubmed
Cuello,
Structural basis for the coupling between activation and inactivation gates in K(+) channels.
2010,
Pubmed
Cummins,
Impaired slow inactivation in mutant sodium channels.
1996,
Pubmed
Drummond,
Reporting ethical matters in the Journal of Physiology: standards and advice.
2009,
Pubmed
Featherstone,
Interaction between fast and slow inactivation in Skm1 sodium channels.
1996,
Pubmed
,
Xenbase
Fleig,
Point mutations in IIS4 alter activation and inactivation of rat brain IIA Na channels in Xenopus oocyte macropatches.
1994,
Pubmed
,
Xenbase
Gellens,
Primary structure and functional expression of the human cardiac tetrodotoxin-insensitive voltage-dependent sodium channel.
1992,
Pubmed
,
Xenbase
Hayward,
Slow inactivation differs among mutant Na channels associated with myotonia and periodic paralysis.
1997,
Pubmed
Jensen,
Orientation and conformation of a lipase at an interface studied by molecular dynamics simulations.
2002,
Pubmed
Jones,
Extracellular proton modulation of the cardiac voltage-gated sodium channel, Nav1.5.
2011,
Pubmed
,
Xenbase
Kehl,
Molecular determinants of the inhibition of human Kv1.5 potassium currents by external protons and Zn(2+).
2002,
Pubmed
Khan,
Isoform-dependent interaction of voltage-gated sodium channels with protons.
2006,
Pubmed
Khan,
Role of outer ring carboxylates of the rat skeletal muscle sodium channel pore in proton block.
2002,
Pubmed
,
Xenbase
Kuzmenkin,
Enhanced inactivation and pH sensitivity of Na(+) channel mutations causing hypokalaemic periodic paralysis type II.
2002,
Pubmed
Makita,
Molecular determinants of beta 1 subunit-induced gating modulation in voltage-dependent Na+ channels.
1996,
Pubmed
,
Xenbase
McCollum,
Negatively charged residues adjacent to IFM motif in the DIII-DIV linker of hNa(V)1.4 differentially affect slow inactivation.
2003,
Pubmed
,
Xenbase
Mitrovic,
Role of domain 4 in sodium channel slow inactivation.
2000,
Pubmed
Nguyen-Thi,
Electrophysiologic effects and electrolyte changes in total myocardial ischemia.
1981,
Pubmed
Noda,
Structure and function of sodium channels.
1993,
Pubmed
Ong,
A structural rearrangement in the sodium channel pore linked to slow inactivation and use dependence.
2000,
Pubmed
Patton,
Amino acid residues required for fast Na(+)-channel inactivation: charge neutralizations and deletions in the III-IV linker.
1992,
Pubmed
Payandeh,
The crystal structure of a voltage-gated sodium channel.
2011,
Pubmed
Payandeh,
Crystal structure of a voltage-gated sodium channel in two potentially inactivated states.
2012,
Pubmed
Terlau,
Mapping the site of block by tetrodotoxin and saxitoxin of sodium channel II.
1991,
Pubmed
,
Xenbase
Todt,
Ultra-slow inactivation in mu1 Na+ channels is produced by a structural rearrangement of the outer vestibule.
1999,
Pubmed
,
Xenbase
Townsend,
Effect of alkali metal cations on slow inactivation of cardiac Na+ channels.
1997,
Pubmed
,
Xenbase
Vilin,
Structural determinants of slow inactivation in human cardiac and skeletal muscle sodium channels.
1999,
Pubmed
,
Xenbase
Vilin,
Slow inactivation in voltage-gated sodium channels: molecular substrates and contributions to channelopathies.
2001,
Pubmed
Vilin,
A single residue differentiates between human cardiac and skeletal muscle Na+ channel slow inactivation.
2001,
Pubmed
,
Xenbase
Vilin,
Acidosis differentially modulates inactivation in na(v)1.2, na(v)1.4, and na(v)1.5 channels.
2012,
Pubmed
Wang,
A mutation in segment I-S6 alters slow inactivation of sodium channels.
1997,
Pubmed
Xiong,
Molecular motions of the outer ring of charge of the sodium channel: do they couple to slow inactivation?
2003,
Pubmed
,
Xenbase
Zhang,
Crystal structure of an orthologue of the NaChBac voltage-gated sodium channel.
2012,
Pubmed
