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Lidocaine induces a slow inactivated state in rat skeletal muscle sodium channels.
Chen Z
,
Ong BH
,
Kambouris NG
,
Marbán E
,
Tomaselli GF
,
Balser JR
.
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1. Local anaesthetics such as lidocaine (lignocaine) interact with sodium channels in a manner that is exquisitely sensitive to the voltage-dependent conformational state of the ion channel. When depolarized in the presence of lidocaine, sodium channels assume a long-lived quiescent state. Although studies over the last decade have localized the lidocaine receptor to the inner aspect of the aqueous pore, the mechanistic basis of depolarization-induced 'use-dependent' lidocaine block remains uncertain. 2. Recent studies have shown that lowering the extracellular Na+ concentration ([Na+]o) and mutations in the sodium channel outer P-loop modulate occupancy of a quiescent 'slow' inactivated state with intermediate kinetics (termed IM) that involves structural rearrangements in the outer pore. 3. Site-directed mutagenesis and ion-replacement experiments were performed using voltage-clamped Xenopus oocytes and cultured (HEK-293) cells expressing wild-type and mutant rat skeletal muscle (mu1) sodium channels. 4. Our results show that lowering [Na+]o potentiates use-dependent lidocaine block. The effect of [Na+]o is maintained despite a III-IV linker mutation that partially disrupts fast inactivation (F1304Q). In contrast, the effect of lowering [Na+]o on lidocaine block is reduced by a P-loop mutation (W402A) that limits occupancy of IM. 5. Our findings are consistent with a simple allosteric model where lidocaine binding induces channels to occupy a native slow inactivated state that is inhibited by [Na+]o.
Adelman,
The effects of external potassium and long duration voltage conditioning on the amplitude of sodium currents in the giant axon of the squid, Loligo pealei.
1969, Pubmed
Adelman,
The effects of external potassium and long duration voltage conditioning on the amplitude of sodium currents in the giant axon of the squid, Loligo pealei.
1969,
Pubmed
Balser,
Global parameter optimization for cardiac potassium channel gating models.
1990,
Pubmed
Balser,
Functional consequences of lidocaine binding to slow-inactivated sodium channels.
1996,
Pubmed
,
Xenbase
Balser,
External pore residue mediates slow inactivation in mu 1 rat skeletal muscle sodium channels.
1996,
Pubmed
,
Xenbase
Balser,
Local anesthetics as effectors of allosteric gating. Lidocaine effects on inactivation-deficient rat skeletal muscle Na channels.
1996,
Pubmed
,
Xenbase
Barber,
Blockade of cardiac sodium channels. Competition between the permeant ion and antiarrhythmic drugs.
1992,
Pubmed
Baukrowitz,
Use-dependent blockers and exit rate of the last ion from the multi-ion pore of a K+ channel.
1996,
Pubmed
Bean,
Lidocaine block of cardiac sodium channels.
1983,
Pubmed
Bennett,
On the molecular nature of the lidocaine receptor of cardiac Na+ channels. Modification of block by alterations in the alpha-subunit III-IV interdomain.
1995,
Pubmed
,
Xenbase
Bénitah,
Molecular motions within the pore of voltage-dependent sodium channels.
1997,
Pubmed
,
Xenbase
Bénitah,
Molecular dynamics of the sodium channel pore vary with gating: interactions between P-segment motions and inactivation.
1999,
Pubmed
,
Xenbase
Cahalan,
Local anesthetic block of sodium channels in normal and pronase-treated squid giant axons.
1978,
Pubmed
Cahalan,
Interactions between quaternary lidocaine, the sodium channel gates, and tetrodotoxin.
1979,
Pubmed
Cannon,
Modification of the Na+ current conducted by the rat skeletal muscle alpha subunit by coexpression with a human brain beta subunit.
1993,
Pubmed
Chandler,
Slow changes in membrane permeability and long-lasting action potentials in axons perfused with fluoride solutions.
1970,
Pubmed
Chang,
Modal behavior of the mu 1 Na+ channel and effects of coexpression of the beta 1-subunit.
1996,
Pubmed
,
Xenbase
Courtney,
Mechanism of frequency-dependent inhibition of sodium currents in frog myelinated nerve by the lidocaine derivative GEA.
1975,
Pubmed
Cummins,
Impaired slow inactivation in mutant sodium channels.
1996,
Pubmed
Fan,
Two human paramyotonia congenita mutations have opposite effects on lidocaine block of Na+ channels expressed in a mammalian cell line.
1996,
Pubmed
Featherstone,
Interaction between fast and slow inactivation in Skm1 sodium channels.
1996,
Pubmed
,
Xenbase
Filatov,
Inactivation and secondary structure in the D4/S4-5 region of the SkM1 sodium channel.
1998,
Pubmed
Grant,
Blockade of cardiac sodium channels by lidocaine. Single-channel analysis.
1989,
Pubmed
HODGKIN,
A quantitative description of membrane current and its application to conduction and excitation in nerve.
1952,
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
Heinemann,
Calcium channel characteristics conferred on the sodium channel by single mutations.
1992,
Pubmed
,
Xenbase
Hille,
Local anesthetics: hydrophilic and hydrophobic pathways for the drug-receptor reaction.
1977,
Pubmed
Hondeghem,
Time- and voltage-dependent interactions of antiarrhythmic drugs with cardiac sodium channels.
1977,
Pubmed
Johns,
Suppression of neuronal and cardiac transient outward currents by viral gene transfer of dominant-negative Kv4.2 constructs.
1997,
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
Lawrence,
Single-channel analysis of inactivation-defective rat skeletal muscle sodium channels containing the F1304Q mutation.
1996,
Pubmed
,
Xenbase
Lerche,
Role in fast inactivation of the IV/S4-S5 loop of the human muscle Na+ channel probed by cysteine mutagenesis.
1997,
Pubmed
Liu,
Dynamic rearrangement of the outer mouth of a K+ channel during gating.
1996,
Pubmed
López-Barneo,
Effects of external cations and mutations in the pore region on C-type inactivation of Shaker potassium channels.
1993,
Pubmed
,
Xenbase
MONOD,
ON THE NATURE OF ALLOSTERIC TRANSITIONS: A PLAUSIBLE MODEL.
1965,
Pubmed
Makielski,
Coexpression of beta 1 with cardiac sodium channel alpha subunits in oocytes decreases lidocaine block.
1996,
Pubmed
,
Xenbase
McPhee,
A mutation in segment IVS6 disrupts fast inactivation of sodium channels.
1994,
Pubmed
,
Xenbase
McPhee,
A critical role for transmembrane segment IVS6 of the sodium channel alpha subunit in fast inactivation.
1995,
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
Nuss,
Isoform-specific lidocaine block of sodium channels explained by differences in gating.
2000,
Pubmed
,
Xenbase
Nuss,
Cardiac sodium channels (hH1) are intrinsically more sensitive to block by lidocaine than are skeletal muscle (mu 1) channels.
1995,
Pubmed
Nuss,
Coupling between fast and slow inactivation revealed by analysis of a point mutation (F1304Q) in mu 1 rat skeletal muscle sodium channels.
1996,
Pubmed
,
Xenbase
Ragsdale,
Molecular determinants of state-dependent block of Na+ channels by local anesthetics.
1994,
Pubmed
,
Xenbase
Ragsdale,
Common molecular determinants of local anesthetic, antiarrhythmic, and anticonvulsant block of voltage-gated Na+ channels.
1996,
Pubmed
Richmond,
Slow inactivation in human cardiac sodium channels.
1998,
Pubmed
,
Xenbase
Rudy,
Slow inactivation of the sodium conductance in squid giant axons. Pronase resistance.
1978,
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
Sunami,
Sodium channel selectivity filter regulates antiarrhythmic drug binding.
1997,
Pubmed
,
Xenbase
Tang,
Glutamine substitution at alanine1649 in the S4-S5 cytoplasmic loop of domain 4 removes the voltage sensitivity of fast inactivation in the human heart sodium channel.
1998,
Pubmed
Todt,
Ultra-slow inactivation in mu1 Na+ channels is produced by a structural rearrangement of the outer vestibule.
1999,
Pubmed
,
Xenbase
Tomaselli,
A mutation in the pore of the sodium channel alters gating.
1995,
Pubmed
,
Xenbase
Townsend,
Effect of alkali metal cations on slow inactivation of cardiac Na+ channels.
1997,
Pubmed
,
Xenbase
Trimmer,
Primary structure and functional expression of a mammalian skeletal muscle sodium channel.
1989,
Pubmed
,
Xenbase
Tsushima,
P-loop flexibility in Na+ channel pores revealed by single- and double-cysteine replacements.
1997,
Pubmed
,
Xenbase
Ukomadu,
muI Na+ channels expressed transiently in human embryonic kidney cells: biochemical and biophysical properties.
1992,
Pubmed
Vedantham,
The position of the fast-inactivation gate during lidocaine block of voltage-gated Na+ channels.
1999,
Pubmed
,
Xenbase
Wang,
Distinct local anesthetic affinities in Na+ channel subtypes.
1996,
Pubmed
Weiner,
A method for the site-directed mono- and multi-mutagenesis of double-stranded DNA.
1993,
Pubmed
West,
A cluster of hydrophobic amino acid residues required for fast Na(+)-channel inactivation.
1992,
Pubmed
,
Xenbase
Yeh,
Sodium inactivation mechanism modulates QX-314 block of sodium channels in squid axons.
1978,
Pubmed
Zhou,
Multiple gating modes and the effect of modulating factors on the microI sodium channel.
1991,
Pubmed
,
Xenbase
Zilberter,
Ca-sensitive slow inactivation and lidocaine-induced block of sodium channels in rat cardiac cells.
1991,
Pubmed
