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.
Cell Mol Neurobiol
2007 Feb 01;271:87-106. doi: 10.1007/s10571-006-9120-2.
Show Gene links
Show Anatomy links
Central charged residues in DIIIS4 regulate deactivation gating in skeletal muscle sodium channels.
Groome JR
,
Alexander HM
,
Fujimoto E
,
Sherry M
,
Petty D
.
???displayArticle.abstract???
1. Mutations in the S4 segment of domain III in the voltage gated skeletal muscle sodium channel hNa(V)1.4 were constructed to test the roles of each charged residue in deactivation gating. Mutations comprised charge reversals at K1-R6, charge neutralization, and substitution at R4 and R5. 2. Charge-reversing mutations at R4 and R5 produced the greatest alteration of activation parameters compared to hNa(V)1.4. Effects included depolarization of the conductance/voltage (g/V) curve, decreased valence and slowing of kinetics. 3. Reversal of charge at R2 to R4 hyperpolarized, and reversal at R5 or R6 depolarized the h (infinity) curve. Most DIIIS4 mutations slowed inactivation from the open state. R4E slowed closed state fast inactivation and R5E inhibited its completion .4. Deactivation from the open and/or inactivated state was prolonged in mutations reversing charge at R2 to R4 but accelerated by reversal of charge at R5 or R6. Effects were most pronounced at central charges R4 and R5. 5. Charge and structure each contribute to effects of mutations at R4 and R5 on channel gating. Effects of mutations on activation and deactivation at R4 and, to a lesser extent R5, were primarily owing to charge alteration, whereas effects on fast inactivation were charge independent.
Armstrong,
Voltage-gated ion channels and electrical excitability.
1998, Pubmed
Armstrong,
Voltage-gated ion channels and electrical excitability.
1998,
Pubmed
Armstrong,
Charge movement associated with the opening and closing of the activation gates of the Na channels.
1974,
Pubmed
Bouhours,
Functional characterization and cold sensitivity of T1313A, a new mutation of the skeletal muscle sodium channel causing paramyotonia congenita in humans.
2004,
Pubmed
Catterall,
From ionic currents to molecular mechanisms: the structure and function of voltage-gated sodium channels.
2000,
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
Dice,
Temperature-sensitive defects in paramyotonia congenita mutants R1448C and T1313M.
2004,
Pubmed
,
Xenbase
Featherstone,
A defect in skeletal muscle sodium channel deactivation exacerbates hyperexcitability in human paramyotonia congenita.
1998,
Pubmed
Groome,
The delay in recovery from fast inactivation in skeletal muscle sodium channels is deactivation.
2000,
Pubmed
,
Xenbase
Groome,
K-aggravated myotonia mutations at residue G1306 differentially alter deactivation gating of human skeletal muscle sodium channels.
2005,
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,
Outer and central charged residues in DIVS4 of skeletal muscle sodium channels have differing roles in deactivation.
2002,
Pubmed
,
Xenbase
Hanck,
Modification of inactivation in cardiac sodium channels: ionic current studies with Anthopleurin-A toxin.
1995,
Pubmed
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,
Immobilizing the moving parts of voltage-gated ion channels.
2000,
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
Kontis,
Sodium channel inactivation is altered by substitution of voltage sensor positive charges.
1997,
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
Lehmann-Horn,
Voltage-gated ion channels and hereditary disease.
1999,
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
Mitrovic,
Independent versus coupled inactivation in sodium channels. Role of the domain 2 S4 segment.
1998,
Pubmed
Noda,
Primary structure of Electrophorus electricus sodium channel deduced from cDNA sequence.
,
Pubmed
Popa,
Cooperative effect of S4-S5 loops in domains D3 and D4 on fast inactivation of the Na+ channel.
2004,
Pubmed
Pusch,
Single point mutations of the sodium channel drastically reduce the pore permeability without preventing its gating.
1991,
Pubmed
,
Xenbase
Sheets,
The Na channel voltage sensor associated with inactivation is localized to the external charged residues of domain IV, S4.
1999,
Pubmed
Sheets,
The role of the putative inactivation lid in sodium channel gating current immobilization.
2000,
Pubmed
Sheets,
Charge immobilization of the voltage sensor in domain IV is independent of sodium current inactivation.
2005,
Pubmed
Sheets,
The outermost lysine in the S4 of domain III contributes little to the gating charge in sodium channels.
2002,
Pubmed
Smith,
Interaction between the sodium channel inactivation linker and domain III S4-S5.
1997,
Pubmed
,
Xenbase
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
Townsend,
Interaction between the pore and a fast gate of the cardiac sodium channel.
1999,
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,
The position of the fourth segment of domain 4 determines status of the inactivation gate in Na+ channels.
2003,
Pubmed
,
Xenbase
Yang,
Evidence for voltage-dependent S4 movement in sodium channels.
1995,
Pubmed
Yu,
Overview of the voltage-gated sodium channel family.
2003,
Pubmed
