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.
A single residue differentiates between human cardiac and skeletal muscle Na+ channel slow inactivation.
Vilin YY
,
Fujimoto E
,
Ruben PC
.
???displayArticle.abstract???
Slow inactivation determines the availability of voltage-gated sodium channels during prolonged depolarization. Slow inactivation in hNa(V)1.4 channels occurs with a higher probability than hNa(V)1.5 sodium channels; however, the precise molecular mechanism for this difference remains unclear. Using the macropatch technique we show that the DII S5-S6 p-region uniquely confers the probability of slow inactivation from parental hNa(V)1.5 and hNa(V)1.4 channels into chimerical constructs expressed in Xenopus oocytes. Site-directed mutagenesis was used to test whether a specific region within DII S5-S6 controls the probability of slow inactivation. We found that substituting V754 in hNa(V)1.4 with isoleucine from the corresponding position (891) in hNa(V)1.5 produced steady-state slow inactivation statistically indistinguishable from that in wild-type hNa(V)1.5 channels, whereas other mutations have little or no effect on slow inactivation. This result indicates that residues V754 in hNa(V)1.4 and I891in hNa(V)1.5 are unique in determining the probability of slow inactivation characteristic of these isoforms. Exchanging S5-S6 linkers between hNa(V)1.4 and hNa(V)1.5 channels had no consistent effect on the voltage-dependent slow time inactivation constants [tau(V)]. This suggests that the molecular structures regulating rates of entry into and exit from the slow inactivated state are different from those controlling the steady-state probability and reside outside the p-regions.
Armstrong,
Inactivation of the sodium channel. II. Gating current experiments.
1977, Pubmed
Armstrong,
Inactivation of the sodium channel. II. Gating current experiments.
1977,
Pubmed
Bezanilla,
Distribution and kinetics of membrane dielectric polarization. 1. Long-term inactivation of gating currents.
1982,
Pubmed
Boland,
Cysteines in the Shaker K+ channel are not essential for channel activity or zinc modulation.
1994,
Pubmed
,
Xenbase
Cannon,
Modification of the Na+ current conducted by the rat skeletal muscle alpha subunit by coexpression with a human brain beta subunit.
1993,
Pubmed
Catterall,
Structure and function of voltage-gated ion channels.
1993,
Pubmed
Cha,
Characterizing voltage-dependent conformational changes in the Shaker K+ channel with fluorescence.
1997,
Pubmed
,
Xenbase
Cha,
Voltage sensors in domains III and IV, but not I and II, are immobilized by Na+ channel fast inactivation.
1999,
Pubmed
,
Xenbase
Chandler,
Slow changes in membrane permeability and long-lasting action potentials in axons perfused with fluoride solutions.
1970,
Pubmed
Chen,
Modulation of Na+ channel inactivation by the beta 1 subunit: a deletion analysis.
1995,
Pubmed
,
Xenbase
Cummins,
Impaired slow inactivation in mutant sodium channels.
1996,
Pubmed
Featherstone,
Interaction between fast and slow inactivation in Skm1 sodium channels.
1996,
Pubmed
,
Xenbase
Fleidervish,
Slow inactivation of Na+ current and slow cumulative spike adaptation in mouse and guinea-pig neocortical neurones in slices.
1996,
Pubmed
Fozzard,
Structure and function of voltage-dependent sodium channels: comparison of brain II and cardiac isoforms.
1996,
Pubmed
Gellens,
Primary structure and functional expression of the human cardiac tetrodotoxin-insensitive voltage-dependent sodium channel.
1992,
Pubmed
,
Xenbase
George,
Primary structure of the adult human skeletal muscle voltage-dependent sodium channel.
1992,
Pubmed
Goldin,
Nomenclature of voltage-gated sodium channels.
2000,
Pubmed
Groome,
Differential effects of homologous S4 mutations in human skeletal muscle sodium channels on deactivation gating from open and inactivated states.
1999,
Pubmed
,
Xenbase
Groome,
The delay in recovery from fast inactivation in skeletal muscle sodium channels is deactivation.
2000,
Pubmed
,
Xenbase
Hartmann,
Effects of III-IV linker mutations on human heart Na+ channel inactivation gating.
1994,
Pubmed
,
Xenbase
Hayward,
Slow inactivation differs among mutant Na channels associated with myotonia and periodic paralysis.
1997,
Pubmed
Ho,
Site-directed mutagenesis by overlap extension using the polymerase chain reaction.
1989,
Pubmed
Hoshi,
Biophysical and molecular mechanisms of Shaker potassium channel inactivation.
1990,
Pubmed
,
Xenbase
Hoshi,
Two types of inactivation in Shaker K+ channels: effects of alterations in the carboxy-terminal region.
1991,
Pubmed
,
Xenbase
Isom,
Primary structure and functional expression of the beta 1 subunit of the rat brain sodium channel.
1992,
Pubmed
,
Xenbase
Isom,
Auxiliary subunits of voltage-gated ion channels.
1994,
Pubmed
Ji,
Paramyotonia congenita mutations reveal different roles for segments S3 and S4 of domain D4 in hSkM1 sodium channel gating.
1996,
Pubmed
Kiss,
Contribution of the selectivity filter to inactivation in potassium channels.
1999,
Pubmed
Kontis,
Sodium channel inactivation is altered by substitution of voltage sensor positive charges.
1997,
Pubmed
,
Xenbase
Liu,
Dynamic rearrangement of the outer mouth of a K+ channel during gating.
1996,
Pubmed
Loots,
Protein rearrangements underlying slow inactivation of the Shaker K+ channel.
1998,
Pubmed
Loots,
Molecular coupling of S4 to a K(+) channel's slow inactivation gate.
2000,
Pubmed
Makita,
Molecular determinants of beta 1 subunit-induced gating modulation in voltage-dependent Na+ channels.
1996,
Pubmed
,
Xenbase
Makita,
Voltage-gated Na+ channel beta 1 subunit mRNA expressed in adult human skeletal muscle, heart, and brain is encoded by a single gene.
1994,
Pubmed
,
Xenbase
Marban,
Structure and function of voltage-gated sodium channels.
1998,
Pubmed
McCormick,
Molecular determinants of Na+ channel function in the extracellular domain of the beta1 subunit.
1998,
Pubmed
,
Xenbase
Mitrovic,
Role of domain 4 in sodium channel slow inactivation.
2000,
Pubmed
O'Reilly,
Comparison of slow inactivation in human heart and rat skeletal muscle Na+ channel chimaeras.
1999,
Pubmed
Patton,
The adult rat brain beta 1 subunit modifies activation and inactivation gating of multiple sodium channel alpha subunits.
1994,
Pubmed
,
Xenbase
Patton,
Amino acid residues required for fast Na(+)-channel inactivation: charge neutralizations and deletions in the III-IV linker.
1992,
Pubmed
Richmond,
Slow inactivation in human cardiac sodium channels.
1998,
Pubmed
,
Xenbase
Rogart,
Molecular cloning of a putative tetrodotoxin-resistant rat heart Na+ channel isoform.
1989,
Pubmed
Ruben,
Holding potential affects the apparent voltage-sensitivity of sodium channel activation in crayfish giant axons.
1990,
Pubmed
Ruben,
Steady-state availability of sodium channels. Interactions between activation and slow inactivation.
1992,
Pubmed
Rudy,
Slow inactivation of the sodium conductance in squid giant axons. Pronase resistance.
1978,
Pubmed
Ruff,
Single-channel basis of slow inactivation of Na+ channels in rat skeletal muscle.
1996,
Pubmed
Ruff,
Slow sodium channel inactivation in mammalian muscle: a possible role in regulating excitability.
1988,
Pubmed
Salgado,
Voltage-dependent removal of sodium inactivation by N-bromoacetamide and pronase.
1985,
Pubmed
Sato,
The sodium channel has four domains surrounding a central pore.
1998,
Pubmed
Sawczuk,
Spike frequency adaptation studied in hypoglossal motoneurons of the rat.
1995,
Pubmed
Sheets,
The role of the putative inactivation lid in sodium channel gating current immobilization.
2000,
Pubmed
Starkus,
Modification of slow sodium inactivation in nerve after internal perfusion with trypsin.
1978,
Pubmed
Toib,
Interaction between duration of activity and time course of recovery from slow inactivation in mammalian brain Na+ channels.
1998,
Pubmed
,
Xenbase
Townsend,
Effect of alkali metal cations on slow inactivation of cardiac Na+ channels.
1997,
Pubmed
,
Xenbase
Trimmer,
Primary structure and functional expression of a mammalian skeletal muscle sodium channel.
1989,
Pubmed
,
Xenbase
Valenzuela,
Gating of cardiac Na+ channels in excised membrane patches after modification by alpha-chymotrypsin.
1994,
Pubmed
Vedantham,
Slow inactivation does not affect movement of the fast inactivation gate in voltage-gated Na+ channels.
1998,
Pubmed
,
Xenbase
Vilin,
Structural determinants of slow inactivation in human cardiac and skeletal muscle sodium channels.
1999,
Pubmed
,
Xenbase
Wang,
A mutation in segment I-S6 alters slow inactivation of sodium channels.
1997,
Pubmed
West,
A cluster of hydrophobic amino acid residues required for fast Na(+)-channel inactivation.
1992,
Pubmed
,
Xenbase
Yang,
How does the W434F mutation block current in Shaker potassium channels?
1997,
Pubmed
,
Xenbase
Yang,
Probing the outer vestibule of a sodium channel voltage sensor.
1997,
Pubmed
Yang,
Expression of the sodium channel beta 1 subunit in rat skeletal muscle is selectively associated with the tetrodotoxin-sensitive alpha subunit isoform.
1993,
Pubmed
Yellen,
An engineered cysteine in the external mouth of a K+ channel allows inactivation to be modulated by metal binding.
1994,
Pubmed
