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We tested the effects of charge-neutralizing mutations of the eight arginine residues in DIVS4 of the rat skeletal muscle sodium channel (rNa(V)1.4) on deactivation gating from the open and inactivated states. We hypothesized that neutralization of outer or central charges would accelerate the I-to-C transition as measured by recovery delay because these represent a portion of the immobilizable charge. R1Q abbreviated recovery delay as a consequence of reduced charge content. R4Q increased delay, whereas R5Q abbreviated delay, and charge-substitutions at these residues indicated that each effect was allosteric. We also hypothesized that neutralization of any residue in DIVS4 would slow the O-to-C transition with reduction in positive charge. Reduction in charge at R1, and to a lesser extent at R5, slowed open-state deactivation, while charge neutralizations at R2, R3, R4, R6, and R7 accelerated open-state deactivation. Our findings suggest that arginine residues in DIVS4 in rNa(V)1.4 have differing roles in channel closure from open and inactivated states. Furthermore, they suggest that deactivation in DIVS4 is regulated by charge interaction between the electrical field with the outermost residue, and by local allosteric interactions imparted by central charges.
Aldrich,
A reinterpretation of mammalian sodium channel gating based on single channel recording.
, Pubmed
Aldrich,
A reinterpretation of mammalian sodium channel gating based on single channel recording.
,
Pubmed Armstrong,
Inactivation of the sodium channel. II. Gating current experiments.
1977,
Pubmed Bendahhou,
Characterization of a new sodium channel mutation at arginine 1448 associated with moderate Paramyotonia congenita in humans.
1999,
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 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 Groome,
The delay in recovery from fast inactivation in skeletal muscle sodium channels is deactivation.
2000,
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 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 Jan,
Maggot's hair and bug's eye: role of cell interactions and intrinsic factors in cell fate specification.
1995,
Pubmed Ji,
Paramyotonia congenita mutations reveal different roles for segments S3 and S4 of domain D4 in hSkM1 sodium channel gating.
1996,
Pubmed Kellenberger,
Movement of the Na+ channel inactivation gate during inactivation.
1996,
Pubmed
,
Xenbase Keynes,
Properties of the voltage sensor for the opening and closing of the sodium channels in the squid giant axon.
1993,
Pubmed Kontis,
Sodium channel inactivation is altered by substitution of voltage sensor positive charges.
1997,
Pubmed
,
Xenbase Kontis,
Sodium channel activation gating is affected by substitutions of voltage sensor positive charges in all four domains.
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 Kuo,
Facilitation of recovery from inactivation by external Na+ and location of the activation gate in neuronal Na+ channels.
2000,
Pubmed Mitrovic,
Role of domain 4 in sodium channel slow inactivation.
2000,
Pubmed Noda,
Primary structure of Electrophorus electricus sodium channel deduced from cDNA sequence.
,
Pubmed Raman,
Inactivation and recovery of sodium currents in cerebellar Purkinje neurons: evidence for two mechanisms.
2001,
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 Stühmer,
Structural parts involved in activation and inactivation of the sodium channel.
1989,
Pubmed
,
Xenbase Trimmer,
Primary structure and functional expression of a mammalian skeletal muscle 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,
Molecular basis of charge movement in voltage-gated sodium channels.
1996,
Pubmed Yang,
Evidence for voltage-dependent S4 movement in sodium channels.
1995,
Pubmed
