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.
Extracellular protons inhibit charge immobilization in the cardiac voltage-gated sodium channel.
Jones DK, Claydon TW, Ruben PC.
???displayArticle.abstract???
Low pH depolarizes the voltage-dependence of cardiac voltage-gated sodium (NaV1.5) channel activation and fast inactivation and destabilizes the fast-inactivated state. The molecular basis for these changes in protein behavior has not been reported. We hypothesized that changes in the kinetics of voltage sensor movement may destabilize the fast-inactivated state in NaV1.5. To test this idea, we recorded NaV1.5 gating currents in Xenopus oocytes using a cut-open voltage-clamp with extracellular solution titrated to either pH 7.4 or pH 6.0. Reducing extracellular pH significantly depolarized the voltage-dependence of both the QON/V and QOFF/V curves, and reduced the total charge immobilized during depolarization. We conclude that destabilized fast-inactivation and reduced charge immobilization in NaV1.5 at low pH are functionally related effects.
Abbruzzese,
Modification of hERG1 channel gating by Cd2+.
2010, Pubmed,
Xenbase
Abbruzzese,
Modification of hERG1 channel gating by Cd2+.
2010,
Pubmed
,
Xenbase Abriel,
Novel arrhythmogenic mechanism revealed by a long-QT syndrome mutation in the cardiac Na(+) channel.
2001,
Pubmed Armstrong,
Inactivation of the sodium channel. II. Gating current experiments.
1977,
Pubmed Bezanilla,
Inactivation of the sodium channel. I. Sodium current experiments.
1977,
Pubmed Campbell,
Sodium channel gating currents in frog skeletal muscle.
1983,
Pubmed Capes,
Gating transitions in the selectivity filter region of a sodium channel are coupled to the domain IV voltage sensor.
2012,
Pubmed Cha,
Voltage sensors in domains III and IV, but not I and II, are immobilized by Na+ channel fast inactivation.
1999,
Pubmed
,
Xenbase Cukierman,
Effects of membrane surface charge and calcium on the gating of rat brain sodium channels in planar bilayers.
1988,
Pubmed Drummond,
Reporting ethical matters in the Journal of Physiology: standards and advice.
2009,
Pubmed Fernandez,
Molecular mapping of a site for Cd2+-induced modification of human ether-à-go-go-related gene (hERG) channel activation.
2005,
Pubmed
,
Xenbase Gellens,
Primary structure and functional expression of the human cardiac tetrodotoxin-insensitive voltage-dependent sodium channel.
1992,
Pubmed
,
Xenbase Groome,
Charge immobilization of skeletal muscle Na+ channels: role of residues in the inactivation linker.
2007,
Pubmed
,
Xenbase Groome,
Open- and closed-state fast inactivation in sodium channels: differential effects of a site-3 anemone toxin.
2011,
Pubmed
,
Xenbase Heggeness,
Saxitoxin and tetrodotoxin. Electrostatic effects on sodium channel gating current in crayfish axons.
1986,
Pubmed Henderson,
Evidence that tetrodotoxin and saxitoxin act at a metal cation binding site in the sodium channels of nerve membrane.
1974,
Pubmed Horn,
Immobilizing the moving parts of voltage-gated ion channels.
2000,
Pubmed Hoshi,
Initial steps in the opening of a Shaker potassium channel.
2012,
Pubmed Jones,
Biophysical defects in voltage.gated sodium channels associated with long QT and Brugada syndromes.
2008,
Pubmed Jones,
Extracellular proton modulation of the cardiac voltage-gated sodium channel, Nav1.5.
2011,
Pubmed
,
Xenbase Jones,
Proton sensors in the pore domain of the cardiac voltage-gated sodium channel.
2013,
Pubmed
,
Xenbase Keynes,
Kinetics and steady-state properties of the charged system controlling sodium conductance in the squid giant axon.
1974,
Pubmed Khan,
Role of outer ring carboxylates of the rat skeletal muscle sodium channel pore in proton block.
2002,
Pubmed
,
Xenbase Khan,
Isoform-dependent interaction of voltage-gated sodium channels with protons.
2006,
Pubmed Kühn,
Movement of voltage sensor S4 in domain 4 is tightly coupled to sodium channel fast inactivation and gating charge immobilization.
1999,
Pubmed
,
Xenbase Long,
Crystal structure of a mammalian voltage-dependent Shaker family K+ channel.
2005,
Pubmed Makita,
Molecular determinants of beta 1 subunit-induced gating modulation in voltage-dependent Na+ channels.
1996,
Pubmed
,
Xenbase 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 Neumcke,
Increased charge displacement in the membrane of myelinated nerve at reduced extracellular pH.
1980,
Pubmed Noda,
Expression of functional sodium channels from cloned cDNA.
,
Pubmed
,
Xenbase 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 Payandeh,
The crystal structure of a voltage-gated sodium channel.
2011,
Pubmed Schauf,
Evidence for negative gating charges in Myxicola axons.
1983,
Pubmed Sheets,
Voltage-dependent open-state inactivation of cardiac sodium channels: gating current studies with Anthopleurin-A toxin.
1995,
Pubmed Sheets,
The role of the putative inactivation lid in sodium channel gating current immobilization.
2000,
Pubmed Sheets,
The Na channel voltage sensor associated with inactivation is localized to the external charged residues of domain IV, S4.
1999,
Pubmed Sheets,
Charge immobilization of the voltage sensor in domain IV is independent of sodium current inactivation.
2005,
Pubmed Starace,
Voltage-dependent proton transport by the voltage sensor of the Shaker K+ channel.
1997,
Pubmed Starace,
Histidine scanning mutagenesis of basic residues of the S4 segment of the shaker k+ channel.
2001,
Pubmed
,
Xenbase Starace,
A proton pore in a potassium channel voltage sensor reveals a focused electric field.
2004,
Pubmed Stühmer,
Structural parts involved in activation and inactivation of the sodium channel.
1989,
Pubmed
,
Xenbase Terlau,
Mapping the site of block by tetrodotoxin and saxitoxin of sodium channel II.
1991,
Pubmed
,
Xenbase Tester,
Compendium of cardiac channel mutations in 541 consecutive unrelated patients referred for long QT syndrome genetic testing.
2005,
Pubmed Wanke,
High intracellular pH reversibly prevents gating-charge immobilization in squid axons.
1983,
Pubmed
