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.
???displayArticle.abstract???
We investigated structural determinants of fast inactivation and deactivation in sodium channels by comparing ionic flux and charge movement in skeletal muscle channels, using mutations of DIII-DIV linker charges. Charge altering and substituting mutations at K-1317, K-1318 depolarized the g(V) curve but hyperpolarized the h(infinity) curve. Charge reversal and substitution at this locus reduced the apparent voltage sensitivity of open- and closed-state fast inactivation. These effects were not observed with charge reversal at E-1314, E-1315. Mutations swapping or neutralizing the negative cluster at 1314, 1315 and the positive cluster at 1317, 1318 indicated that local interactions dictate the coupling of activation to fast inactivation. Gating charge was immobilized before channel entry into fast inactivation in hNa(V)1.4 but to a lesser extent in mutations at K-1317, K-1318. These results suggest that charge is preferentially immobilized in channels inactivating from the open state. Recovery of gating charge proceeded with a single, fast phase in the double mutation K-1317R, K-1318R. This mutation also partially uncoupled recovery from deactivation. Our findings indicate that charged residues near the fast inactivation "particle" allosterically interact with voltage sensors to control aspects of gating in sodium channels.
Aldrich,
Voltage-dependent gating of single sodium channels from mammalian neuroblastoma cells.
1987, Pubmed
Aldrich,
Voltage-dependent gating of single sodium channels from mammalian neuroblastoma cells.
1987,
Pubmed
Armstrong,
Voltage-gated ion channels and electrical excitability.
1998,
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
Catterall,
From ionic currents to molecular mechanisms: the structure and function of voltage-gated sodium channels.
2000,
Pubmed
Cestèle,
Structure and function of the voltage sensor of sodium channels probed by a beta-scorpion toxin.
2006,
Pubmed
Cha,
Voltage sensors in domains III and IV, but not I and II, are immobilized by Na+ channel fast inactivation.
1999,
Pubmed
,
Xenbase
Chahine,
Sodium channel mutations in paramyotonia congenita uncouple inactivation from activation.
1994,
Pubmed
Chanda,
Tracking voltage-dependent conformational changes in skeletal muscle sodium channel during activation.
2002,
Pubmed
,
Xenbase
Chen,
A unique role for the S4 segment of domain 4 in the inactivation of sodium channels.
1996,
Pubmed
,
Xenbase
Cota,
Sodium channel gating in clonal pituitary cells. The inactivation step is not voltage dependent.
1989,
Pubmed
Featherstone,
A defect in skeletal muscle sodium channel deactivation exacerbates hyperexcitability in human paramyotonia congenita.
1998,
Pubmed
Filatov,
Inactivation and secondary structure in the D4/S4-5 region of the SkM1 sodium channel.
1998,
Pubmed
Gallivan,
Cation-pi interactions in structural biology.
1999,
Pubmed
Goldin,
Nomenclature of voltage-gated sodium channels.
2000,
Pubmed
Groome,
Negative charges in the DIII-DIV linker of human skeletal muscle Na+ channels regulate deactivation gating.
2003,
Pubmed
,
Xenbase
Groome,
Central charged residues in DIIIS4 regulate deactivation gating in skeletal muscle sodium channels.
2007,
Pubmed
,
Xenbase
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
Groome,
Outer and central charged residues in DIVS4 of skeletal muscle sodium channels have differing roles in deactivation.
2002,
Pubmed
,
Xenbase
Ho,
Site-directed mutagenesis by overlap extension using the polymerase chain reaction.
1989,
Pubmed
HODGKIN,
A quantitative description of membrane current and its application to conduction and excitation in nerve.
1952,
Pubmed
Horn,
Statistical properties of single sodium channels.
1984,
Pubmed
Horn,
Immobilizing the moving parts of voltage-gated ion channels.
2000,
Pubmed
Ji,
Paramyotonia congenita mutations reveal different roles for segments S3 and S4 of domain D4 in hSkM1 sodium channel gating.
1996,
Pubmed
Kellenberger,
Molecular analysis of potential hinge residues in the inactivation gate of brain type IIA Na+ channels.
1997,
Pubmed
Kontis,
Sodium channel activation gating is affected by substitutions of voltage sensor positive charges in all four domains.
1997,
Pubmed
,
Xenbase
Kühn,
Mutation D384N alters recovery of the immobilized gating charge in rat brain IIA sodium channels.
2002,
Pubmed
,
Xenbase
Kühn,
Movement of voltage sensor S4 in domain 4 is tightly coupled to sodium channel fast inactivation and gating charge immobilization.
1999,
Pubmed
,
Xenbase
Kuo,
Na+ channels must deactivate to recover from inactivation.
1994,
Pubmed
Lerche,
Role in fast inactivation of the IV/S4-S5 loop of the human muscle Na+ channel probed by cysteine mutagenesis.
1997,
Pubmed
McPhee,
A critical role for the S4-S5 intracellular loop in domain IV of the sodium channel alpha-subunit in fast inactivation.
1998,
Pubmed
,
Xenbase
Meves,
Inactivation of the asymmetrical displacement current in giant axons of Loligo forbesi.
1977,
Pubmed
Miller,
Contributions of charged residues in a cytoplasmic linking region to Na channel gating.
2000,
Pubmed
,
Xenbase
Mitrovic,
Independent versus coupled inactivation in sodium channels. Role of the domain 2 S4 segment.
1998,
Pubmed
Moorman,
Changes in sodium channel gating produced by point mutations in a cytoplasmic linker.
1990,
Pubmed
Noda,
Primary structure of Electrophorus electricus sodium channel deduced from cDNA sequence.
,
Pubmed
O'Leary,
A molecular link between activation and inactivation of sodium channels.
1995,
Pubmed
Patton,
Amino acid residues required for fast Na(+)-channel inactivation: charge neutralizations and deletions in the III-IV linker.
1992,
Pubmed
Popa,
Cooperative effect of S4-S5 loops in domains D3 and D4 on fast inactivation of the Na+ channel.
2004,
Pubmed
Rohl,
Solution structure of the sodium channel inactivation gate.
1999,
Pubmed
Santarelli,
A cation-pi interaction discriminates among sodium channels that are either sensitive or resistant to tetrodotoxin block.
2007,
Pubmed
,
Xenbase
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
Smith,
Interaction between the sodium channel inactivation linker and domain III S4-S5.
1997,
Pubmed
,
Xenbase
Stimers,
Sodium channel activation in the squid giant axon. Steady state properties.
1985,
Pubmed
Stühmer,
Structural parts involved in activation and inactivation of the sodium channel.
1989,
Pubmed
,
Xenbase
Tang,
Role of an S4-S5 linker in sodium channel inactivation probed by mutagenesis and a peptide blocker.
1996,
Pubmed
Vassilev,
Identification of an intracellular peptide segment involved in sodium channel inactivation.
1988,
Pubmed
West,
A cluster of hydrophobic amino acid residues required for fast Na(+)-channel inactivation.
1992,
Pubmed
,
Xenbase
Yang,
Molecular basis of charge movement in voltage-gated sodium channels.
1996,
Pubmed
Yang,
Evidence for voltage-dependent S4 movement in sodium channels.
1995,
Pubmed
Yu,
Overview of the voltage-gated sodium channel family.
2003,
Pubmed
