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Rapid and slow voltage-dependent conformational changes in segment IVS6 of voltage-gated Na(+) channels.
Vedantham V
,
Cannon SC
.
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Mutations in segment IVS6 of voltage-gated Na(+) channels affect fast-inactivation, slow-inactivation, local anesthetic action, and batrachotoxin (BTX) action. To detect conformational changes associated with these processes, we substituted a cysteine for a valine at position 1583 in the rat adult skeletal muscle sodium channel alpha-subunit, and examined the accessibility of the substituted cysteine to modification by 2-aminoethyl methanethiosulfonate (MTS-EA) in excised macropatches. MTS-EA causes an irreversible reduction in the peak current when applied both internally and externally, with a reaction rate that is strongly voltage-dependent. The rate increased when exposures to MTS-EA occurred during brief conditioning pulses to progressively more depolarized voltages, but decreased when exposures occurred at the end of prolonged depolarizations, revealing two conformational changes near site 1583, one coupled to fast inactivation, and one tightly associated with slow inactivation. Tetraethylammonium, a pore blocker, did not affect the reaction rate from either direction, while BTX, a lipophilic activator of sodium channels, completely prevented the modification reaction from occurring from either direction. We conclude that there are two inactivation-associated conformational changes in the vicinity of site 1583, that the reactive site most likely faces away from the pore, and that site 1583 comprises part of the BTX receptor.
Balser,
External pore residue mediates slow inactivation in mu 1 rat skeletal muscle sodium channels.
1996, Pubmed,
Xenbase
Balser,
External pore residue mediates slow inactivation in mu 1 rat skeletal muscle sodium channels.
1996,
Pubmed
,
Xenbase
Bénitah,
Molecular dynamics of the sodium channel pore vary with gating: interactions between P-segment motions and inactivation.
1999,
Pubmed
,
Xenbase
Cannon,
Functional expression of sodium channel mutations identified in families with periodic paralysis.
1993,
Pubmed
Cha,
Voltage sensors in domains III and IV, but not I and II, are immobilized by Na+ channel fast inactivation.
1999,
Pubmed
,
Xenbase
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
Hayward,
Inactivation defects caused by myotonia-associated mutations in the sodium channel III-IV linker.
1996,
Pubmed
Hayward,
Slow inactivation differs among mutant Na channels associated with myotonia and periodic paralysis.
1997,
Pubmed
Hille,
Local anesthetics: hydrophilic and hydrophobic pathways for the drug-receptor reaction.
1977,
Pubmed
Holmgren,
On the use of thiol-modifying agents to determine channel topology.
1996,
Pubmed
,
Xenbase
Holmgren,
The activation gate of a voltage-gated K+ channel can be trapped in the open state by an intersubunit metal bridge.
1998,
Pubmed
Jan,
A superfamily of ion channels.
1990,
Pubmed
Kambouris,
Mechanistic link between lidocaine block and inactivation probed by outer pore mutations in the rat micro1 skeletal muscle sodium channel.
1998,
Pubmed
,
Xenbase
Kellenberger,
Movement of the Na+ channel inactivation gate during inactivation.
1996,
Pubmed
,
Xenbase
Khodorov,
Batrachotoxin as a tool to study voltage-sensitive sodium channels of excitable membranes.
1985,
Pubmed
Liman,
Subunit stoichiometry of a mammalian K+ channel determined by construction of multimeric cDNAs.
1992,
Pubmed
,
Xenbase
Linford,
Interaction of batrachotoxin with the local anesthetic receptor site in transmembrane segment IVS6 of the voltage-gated sodium channel.
1998,
Pubmed
Liu,
Gated access to the pore of a voltage-dependent K+ channel.
1997,
Pubmed
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
McClatchey,
The cloning and expression of a sodium channel beta 1-subunit cDNA from human brain.
1993,
Pubmed
,
Xenbase
McPhee,
A critical role for transmembrane segment IVS6 of the sodium channel alpha subunit in fast inactivation.
1995,
Pubmed
McPhee,
A mutation in segment IVS6 disrupts fast inactivation of sodium channels.
1994,
Pubmed
,
Xenbase
O'Leary,
Internal block of human heart sodium channels by symmetrical tetra-alkylammoniums.
1994,
Pubmed
Perozo,
Structural rearrangements underlying K+-channel activation gating.
1999,
Pubmed
Ragsdale,
Molecular determinants of state-dependent block of Na+ channels by local anesthetics.
1994,
Pubmed
,
Xenbase
Takahashi,
Enhanced slow inactivation by V445M: a sodium channel mutation associated with myotonia.
1999,
Pubmed
Tanguy,
BTX modification of Na channels in squid axons. I. State dependence of BTX action.
1991,
Pubmed
Todt,
Ultra-slow inactivation in mu1 Na+ channels is produced by a structural rearrangement of the outer vestibule.
1999,
Pubmed
,
Xenbase
Townsend,
Effect of alkali metal cations on slow inactivation of cardiac Na+ channels.
1997,
Pubmed
,
Xenbase
Trainer,
Site of covalent labeling by a photoreactive batrachotoxin derivative near transmembrane segment IS6 of the sodium channel alpha subunit.
1996,
Pubmed
Vedantham,
The position of the fast-inactivation gate during lidocaine block of voltage-gated Na+ channels.
1999,
Pubmed
,
Xenbase
Vedantham,
Slow inactivation does not affect movement of the fast inactivation gate in voltage-gated Na+ channels.
1998,
Pubmed
,
Xenbase
Wang,
Point mutations in segment I-S6 render voltage-gated Na+ channels resistant to batrachotoxin.
1998,
Pubmed
Wang,
Batrachotoxin-resistant Na+ channels derived from point mutations in transmembrane segment D4-S6.
1999,
Pubmed
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
Wright,
Lysine point mutations in Na+ channel D4-S6 reduce inactivated channel block by local anesthetics.
1998,
Pubmed
Yang,
Evidence for voltage-dependent S4 movement in sodium channels.
1995,
Pubmed
Yang,
Molecular basis of charge movement in voltage-gated sodium channels.
1996,
Pubmed
