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Fast inactivation and deactivation gating were compared between wild-type human voltage-gated skeletal muscle sodium channel (hNaV1.4) and potassium-aggravated myotonia (PAM) mutations G1306A, G1306E, and G1306V. Cell-attached macropatches were used to compare wild-type and PAM-gating properties in normal extracellular K+ (4 mM), decreased K+ (1 mM), and increased K+ (10 mM). G1306E/A increased the apparent valence of the conductance (g(V)) curve. Compared to hNaV1.4, the steady-state inactivation (h infinity) curve was depolarized for G1306E/A but hyperpolarized by G1306V, and this mutation increased apparent valence. G1306A/E slowed the rate of current rise towards peak activation. G1306V slowed open-state deactivation, inactivated-state deactivation, and recovery from fast inactivation. G1306A/E abbreviated open-state deactivation at negative commands. These mutants slowed open-state deactivation at more positive commands, at voltages for which fast inactivation might influence tail current decay. G1306E abbreviated recovery delay without affecting recovery rate. Low K+ increased peak current in hNaV1.4 and in G1306V. For G1306E, low K+ increased the rate of entry into fast inactivation, hyperpolarized the g(V) and h(infinity) curves, and increased recovery delay. Biophysical underpinnings of PAM caused by mutations of G1306 thus vary with the specific mutation, and hyperkalemic exacerbation of effects of mutations at this residue are not direct.
Bouhours,
Functional characterization and cold sensitivity of T1313A, a new mutation of the skeletal muscle sodium channel causing paramyotonia congenita in humans.
2004, 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 Cannon,
Spectrum of sodium channel disturbances in the nondystrophic myotonias and periodic paralyses.
2000,
Pubmed Cannon,
From mutation to myotonia in sodium channel disorders.
1997,
Pubmed Catterall,
From ionic currents to molecular mechanisms: the structure and function of voltage-gated sodium channels.
2000,
Pubmed Chahine,
Sodium channel mutations in paramyotonia congenita uncouple inactivation from activation.
1994,
Pubmed 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 George,
Primary structure of the adult human skeletal muscle voltage-dependent sodium channel.
1992,
Pubmed George,
Molecular genetics of ion channel diseases.
1995,
Pubmed Green,
Human sodium channel gating defects caused by missense mutations in S6 segments associated with myotonia: S804F and V1293I.
1998,
Pubmed Groome,
The delay in recovery from fast inactivation in skeletal muscle sodium channels is deactivation.
2000,
Pubmed
,
Xenbase Groome,
Negative charges in the DIII-DIV linker of human skeletal muscle Na+ channels regulate deactivation gating.
2003,
Pubmed
,
Xenbase Groome,
Outer and central charged residues in DIVS4 of skeletal muscle sodium channels have differing roles in deactivation.
2002,
Pubmed
,
Xenbase Hayward,
Inactivation defects caused by myotonia-associated mutations in the sodium channel III-IV linker.
1996,
Pubmed Heine,
A novel SCN4A mutation causing myotonia aggravated by cold and potassium.
1993,
Pubmed Ho,
Site-directed mutagenesis by overlap extension using the polymerase chain reaction.
1989,
Pubmed Hoffman,
Overexcited or inactive: ion channels in muscle disease.
1995,
Pubmed Horn,
Immobilizing the moving parts of voltage-gated ion channels.
2000,
Pubmed Isom,
Auxiliary subunits of voltage-gated ion channels.
1994,
Pubmed Kuo,
Na+ channels must deactivate to recover from inactivation.
1994,
Pubmed Lehmann-Horn,
Voltage-gated ion channels and hereditary disease.
1999,
Pubmed Lerche,
[Ion channel diseases in neurology].
1997,
Pubmed Lerche,
Human sodium channel myotonia: slowed channel inactivation due to substitutions for a glycine within the III-IV linker.
1993,
Pubmed McClatchey,
Novel mutations in families with unusual and variable disorders of the skeletal muscle sodium channel.
1992,
Pubmed Mitrović,
K(+)-aggravated myotonia: destabilization of the inactivated state of the human muscle Na+ channel by the V1589M mutation.
1994,
Pubmed Mitrović,
Different effects on gating of three myotonia-causing mutations in the inactivation gate of the human muscle sodium channel.
1995,
Pubmed Moran,
Myopathic mutations affect differently the inactivation of the two gating modes of sodium channels.
1999,
Pubmed
,
Xenbase Noda,
Primary structure of Electrophorus electricus sodium channel deduced from cDNA sequence.
,
Pubmed Orrell,
Familial cramp due to potassium-aggravated myotonia.
1998,
Pubmed Peter,
A human muscle Na+ channel mutation in the voltage sensor IV/S4 affects channel block by the pentapeptide KIFMK.
1999,
Pubmed Ptacek,
Sodium channel mutations in paramyotonia congenita and hyperkalemic periodic paralysis.
1993,
Pubmed Ptáĉek,
Sodium channel mutations in acetazolamide-responsive myotonia congenita, paramyotonia congenita, and hyperkalemic periodic paralysis.
1994,
Pubmed Richmond,
Defective fast inactivation recovery and deactivation account for sodium channel myotonia in the I1160V mutant.
1997,
Pubmed
,
Xenbase Rosenfeld,
A novel muscle sodium channel mutation causes painful congenital myotonia.
1997,
Pubmed Rüdel,
Abnormalities of the fast sodium current in myotonic dystrophy, recessive generalized myotonia, and adynamia episodica.
1989,
Pubmed Stühmer,
Structural parts involved in activation and inactivation of the sodium channel.
1989,
Pubmed
,
Xenbase 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,
Evidence for voltage-dependent S4 movement in sodium channels.
1995,
Pubmed
