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.
Biophys J
2011 Nov 02;1019:2147-56. doi: 10.1016/j.bpj.2011.08.056.
Show Gene links
Show Anatomy links
Extracellular proton modulation of the cardiac voltage-gated sodium channel, Nav1.5.
Jones DK
,
Peters CH
,
Tolhurst SA
,
Claydon TW
,
Ruben PC
.
???displayArticle.abstract???
Low pH depolarizes the voltage dependence of voltage-gated sodium (Na(V)) channel activation and fast inactivation. A complete description of Na(V) channel proton modulation, however, has not been reported. The majority of Na(V) channel proton modulation studies have been completed in intact tissue. Additionally, several Na(V) channel isoforms are expressed in cardiac tissue. Characterizing the proton modulation of the cardiac Na(V) channel, Na(V)1.5, will thus help define its contribution to ischemic arrhythmogenesis, where extracellular pH drops from pH 7.4 to as low as pH 6.0 within ~10 min of its onset. We expressed the human variant of Na(V)1.5 with and without the modulating β(1) subunit in Xenopus oocytes. Lowering extracellular pH from 7.4 to 6.0 affected a range of biophysical gating properties heretofore unreported. Specifically, acidic pH destabilized the fast-inactivated and slow-inactivated states, and elevated persistent I(Na). These data were incorporated into a ventricular action potential model that displayed a reduced maximum rate of depolarization as well as disparate increases in epicardial, mid-myocardial, and endocardial action potential durations, indicative of an increased heterogeneity of repolarization. Portions of these data were previously reported in abstract form.
Antzelevitch,
The role of sodium channel current in modulating transmural dispersion of repolarization and arrhythmogenesis.
2006, Pubmed
Antzelevitch,
The role of sodium channel current in modulating transmural dispersion of repolarization and arrhythmogenesis.
2006,
Pubmed
Antzelevitch,
Does Tpeak-Tend provide an index of transmural dispersion of repolarization?
2007,
Pubmed
Anumonwo,
Proton and zinc effects on HERG currents.
1999,
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
Begenisich,
Hydrogen ion block of the sodium pore in squid giant axons.
1983,
Pubmed
Campbell,
Altered sodium and gating current kinetics in frog skeletal muscle caused by low external pH.
1984,
Pubmed
Cha,
Voltage sensors in domains III and IV, but not I and II, are immobilized by Na+ channel fast inactivation.
1999,
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
Crampin,
Acidosis in models of cardiac ventricular myocytes.
2006,
Pubmed
Daumas,
Proton block of rat brain sodium channels. Evidence for two proton binding sites and multiple occupancy.
1993,
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
Gellens,
Primary structure and functional expression of the human cardiac tetrodotoxin-insensitive voltage-dependent sodium channel.
1992,
Pubmed
,
Xenbase
Hille,
Charges and potentials at the nerve surface. Divalent ions and pH.
1968,
Pubmed
Hund,
Rate dependence and regulation of action potential and calcium transient in a canine cardiac ventricular cell model.
2004,
Pubmed
Jones,
Biophysical defects in voltage.gated sodium channels associated with long QT and Brugada syndromes.
2008,
Pubmed
Ju,
Hypoxia increases persistent sodium current in rat ventricular myocytes.
1996,
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
Lubinski,
New insight into repolarization abnormalities in patients with congenital long QT syndrome: the increased transmural dispersion of repolarization.
1998,
Pubmed
Luo,
A dynamic model of the cardiac ventricular action potential. I. Simulations of ionic currents and concentration changes.
1994,
Pubmed
Luo,
A dynamic model of the cardiac ventricular action potential. II. Afterdepolarizations, triggered activity, and potentiation.
1994,
Pubmed
Makita,
Molecular determinants of beta 1 subunit-induced gating modulation in voltage-dependent Na+ channels.
1996,
Pubmed
,
Xenbase
Malhotra,
Sodium channel beta subunits mediate homophilic cell adhesion and recruit ankyrin to points of cell-cell contact.
2000,
Pubmed
Maltsev,
Late Na+ current produced by human cardiac Na+ channel isoform Nav1.5 is modulated by its beta1 subunit.
2009,
Pubmed
Meadows,
The intracellular segment of the sodium channel beta 1 subunit is required for its efficient association with the channel alpha subunit.
2001,
Pubmed
,
Xenbase
Murphy,
Extracellular proton depression of peak and late Na⁺ current in the canine left ventricle.
2011,
Pubmed
Nagatomo,
Temperature dependence of early and late currents in human cardiac wild-type and long Q-T DeltaKPQ Na+ channels.
1998,
Pubmed
Nguyen-Thi,
Electrophysiologic effects and electrolyte changes in total myocardial ischemia.
1981,
Pubmed
Noda,
Primary structure of Electrophorus electricus sodium channel deduced from cDNA sequence.
,
Pubmed
Patton,
Amino acid residues required for fast Na(+)-channel inactivation: charge neutralizations and deletions in the III-IV linker.
1992,
Pubmed
Qu,
Modulation of cardiac Na+ channel expression in Xenopus oocytes by beta 1 subunits.
1995,
Pubmed
,
Xenbase
Richmond,
Slow inactivation in human cardiac sodium channels.
1998,
Pubmed
,
Xenbase
Sigworth,
The conductance of sodium channels under conditions of reduced current at the node of Ranvier.
1980,
Pubmed
Stühmer,
Structural parts involved in activation and inactivation of the sodium channel.
1989,
Pubmed
,
Xenbase
Ten Tusscher,
Cell model for efficient simulation of wave propagation in human ventricular tissue under normal and pathological conditions.
2006,
Pubmed
Terlau,
Mapping the site of block by tetrodotoxin and saxitoxin of sodium channel II.
1991,
Pubmed
,
Xenbase
Terrenoire,
Autonomic control of cardiac action potentials: role of potassium channel kinetics in response to sympathetic stimulation.
2005,
Pubmed
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
Woodhull,
Ionic blockage of sodium channels in nerve.
1973,
Pubmed
Xiong,
Molecular motions of the outer ring of charge of the sodium channel: do they couple to slow inactivation?
2003,
Pubmed
,
Xenbase
Yatani,
Effect of extracellular pH on sodium current in isolated, single rat ventricular cells.
1984,
Pubmed
Zygmunt,
Larger late sodium conductance in M cells contributes to electrical heterogeneity in canine ventricle.
2001,
Pubmed
ten Tusscher,
Alternans and spiral breakup in a human ventricular tissue model.
2006,
Pubmed
ten Tusscher,
A model for human ventricular tissue.
2004,
Pubmed
