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Post-repolarization block of cloned sodium channels by saxitoxin: the contribution of pore-region amino acids.
Satin J
,
Kyle JW
,
Fan Z
,
Rogart R
,
Fozzard HA
,
Makielski JC
.
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Sodium channels expressed in oocytes exhibited isoform differences in phasic block by saxitoxin (STX). Neuronal channels (rat IIa co-expressed with beta 1 subunit, Br2a + beta 1) had slower kinetics of phasic block for pulse trains than cardiac channels (RHI). After the membrane was repolarized from a single brief depolarizing step, a test pulse at increasing intervals showed first a decrease in current (post-repolarization block) then eventual recovery in the presence of STX. This block/unblock process for Br2a + beta 1 was 10-fold slower than that for RHI. A model accounting for these results predicts a faster toxin dissociation rate and a slower association rate for the cardiac isoform, and it also predicts a shorter dwell time in a putative high STX affinity conformation for the cardiac isoform. The RHI mutation (Cys374-->Phe), which was previously shown to be neuronal-like with respect to high affinity tonic toxin block, was also neuronal-like with respect to the kinetics of post-repolarization block, suggesting that this single amino acid is important for conferring isoform-specific transition rates determining post-repolarization block. Because the same mutation determines both sensitivity for tonic STX block and the kinetics of phasic STX block, the mechanisms accounting for tonic block and phasic block share the same toxin binding site. We conclude that the residue at position 374, in the putative pore-forming region, confers isoform-specific channel kinetics that underlie phasic toxin block.
Armstrong,
Charge movement associated with the opening and closing of the activation gates of the Na channels.
1974, Pubmed
Armstrong,
Charge movement associated with the opening and closing of the activation gates of the Na channels.
1974,
Pubmed
Backx,
Molecular localization of an ion-binding site within the pore of mammalian sodium channels.
1992,
Pubmed
Baer,
Voltage-dependent action of tetrodotoxin in mammalian cardiac muscle.
1976,
Pubmed
Barish,
A transient calcium-dependent chloride current in the immature Xenopus oocyte.
1983,
Pubmed
,
Xenbase
Butterworth,
Molecular mechanisms of local anesthesia: a review.
1990,
Pubmed
Carmeliet,
Voltage-dependent block by tetrodotoxin of the sodium channel in rabbit cardiac Purkinje fibers.
1987,
Pubmed
Clarkson,
Evidence for voltage-dependent block of cardiac sodium channels by tetrodotoxin.
1988,
Pubmed
Cohen,
Tetrodotoxin block of sodium channels in rabbit Purkinje fibers. Interactions between toxin binding and channel gating.
1981,
Pubmed
Cribbs,
Functional expression of the rat heart I Na+ channel isoform. Demonstration of properties characteristic of native cardiac Na+ channels.
1990,
Pubmed
,
Xenbase
Doyle,
Divalent cation competition with [3H]saxitoxin binding to tetrodotoxin-resistant and -sensitive sodium channels. A two-site structural model of ion/toxin interaction.
1993,
Pubmed
Eickhorn,
Use dependence of sodium current inhibition by tetrodotoxin in rat cardiac muscle: influence of channel state.
1990,
Pubmed
Guo,
Kinetic basis for insensitivity to tetrodotoxin and saxitoxin in sodium channels of canine heart and denervated rat skeletal muscle.
1987,
Pubmed
Guy,
Pursuing the structure and function of voltage-gated channels.
1990,
Pubmed
,
Xenbase
Hanck,
Gating currents associated with Na channels in canine cardiac Purkinje cells.
1990,
Pubmed
Heinemann,
Calcium channel characteristics conferred on the sodium channel by single mutations.
1992,
Pubmed
,
Xenbase
Heinemann,
Molecular basis for pharmacological differences between brain and cardiac sodium channels.
1992,
Pubmed
Hille,
Local anesthetics: hydrophilic and hydrophobic pathways for the drug-receptor reaction.
1977,
Pubmed
Inoue,
Block of avian cardiac fast sodium channels by tetrodotoxin is enhanced by repetitive depolarization but not by steady depolarization.
1984,
Pubmed
Isom,
Primary structure and functional expression of the beta 1 subunit of the rat brain sodium channel.
1992,
Pubmed
,
Xenbase
Krueger,
Single sodium channels from rat brain incorporated into planar lipid bilayer membranes.
,
Pubmed
Lipkind,
A structural model of the tetrodotoxin and saxitoxin binding site of the Na+ channel.
1994,
Pubmed
Lönnendonker,
Use-dependent block with tetrodotoxin and saxitoxin at frog Ranvier nodes. II. Extrinsic influence of cations.
1991,
Pubmed
Lönnendonker,
Use-dependent block of sodium channels in frog myelinated nerve by tetrodotoxin and saxitoxin at negative holding potentials.
1989,
Pubmed
Makielski,
Post-repolarization block of cardiac sodium channels by saxitoxin.
1993,
Pubmed
Noda,
A single point mutation confers tetrodotoxin and saxitoxin insensitivity on the sodium channel II.
1989,
Pubmed
,
Xenbase
Patton,
A voltage-dependent gating transition induces use-dependent block by tetrodotoxin of rat IIA sodium channels expressed in Xenopus oocytes.
1991,
Pubmed
,
Xenbase
Quandt,
All or none block of single Na+ channels by tetrodotoxin.
1985,
Pubmed
Salgado,
Use- and voltage-dependent block of the sodium channel by saxitoxin.
1986,
Pubmed
Satin,
A mutant of TTX-resistant cardiac sodium channels with TTX-sensitive properties.
1992,
Pubmed
,
Xenbase
Satin,
The cloned cardiac Na channel alpha-subunit expressed in Xenopus oocytes show gating and blocking properties of native channels.
1992,
Pubmed
,
Xenbase
Scanley,
Kinetic analysis of single sodium channels from canine cardiac Purkinje cells.
1990,
Pubmed
Trimmer,
Primary structure and functional expression of a mammalian skeletal muscle sodium channel.
1989,
Pubmed
,
Xenbase
Vandenberg,
Single-channel, macroscopic, and gating currents from sodium channels in the squid giant axon.
1991,
Pubmed
Vassilev,
Voltage-dependent action of tetrodotoxin in mammalian cardiac myocytes.
1986,
Pubmed
