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J Comp Physiol A Neuroethol Sens Neural Behav Physiol
2011 Jan 01;1971:33-43. doi: 10.1007/s00359-010-0582-9.
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Biophysical costs associated with tetrodotoxin resistance in the sodium channel pore of the garter snake, Thamnophis sirtalis.
Lee CH
,
Jones DK
,
Ahern C
,
Sarhan MF
,
Ruben PC
.
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Tetrodotoxin (TTX) is a potent toxin that specifically binds to voltage-gated sodium channels (NaV). TTX binding physically blocks the flow of sodium ions through NaV, thereby preventing action potential generation and propagation. TTX has different binding affinities for different NaV isoforms. These differences are imparted by amino acid substitutions in positions within, or proximal to, the TTX-binding site in the channel pore. These substitutions confer TTX-resistance to a variety of species. The garter snake Thamnophis sirtalis has evolved TTX-resistance over the course of an armsrace, allowing some populations of snakes to feed on tetrodotoxic newts, including Taricha granulosa. Different populations of the garter snake have different degrees of TTX-resistance, which is closely related to the number of amino acid substitutions. We tested the biophysical properties and ion selectivity of NaV of three garter snake populations from Bear Lake, Idaho; Warrenton, Oregon; and Willow Creek, California. We observed changes in gating properties of TTX-resistant (TTXr) NaV. In addition, ion selectivity of TTXr NaV was significantly different from that of TTX-sensitive NaV. These results suggest TTX-resistance comes at a cost to performance caused by changes in the biophysical properties and ion selectivity of TTXr NaV.
Armstrong,
Na channel inactivation from open and closed states.
2006, Pubmed
Armstrong,
Na channel inactivation from open and closed states.
2006,
Pubmed
Bezanilla,
How membrane proteins sense voltage.
2008,
Pubmed
Brodie,
COSTS OF EXPLOITING POISONOUS PREY: EVOLUTIONARY TRADE-OFFS IN A PREDATOR-PREY ARMS RACE.
1999,
Pubmed
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
Catterall,
International Union of Pharmacology. XLVII. Nomenclature and structure-function relationships of voltage-gated sodium channels.
2005,
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,
Functional expression and properties of the human skeletal muscle sodium channel.
1994,
Pubmed
,
Xenbase
Chanda,
Coupling interactions between voltage sensors of the sodium channel as revealed by site-specific measurements.
2004,
Pubmed
Chanda,
Tracking voltage-dependent conformational changes in skeletal muscle sodium channel during activation.
2002,
Pubmed
,
Xenbase
Chang,
Predominant interactions between mu-conotoxin Arg-13 and the skeletal muscle Na+ channel localized by mutant cycle analysis.
1998,
Pubmed
,
Xenbase
Chiamvimonvat,
Control of ion flux and selectivity by negatively charged residues in the outer mouth of rat sodium channels.
1996,
Pubmed
,
Xenbase
Choudhary,
Interactions of the C-11 hydroxyl of tetrodotoxin with the sodium channel outer vestibule.
2003,
Pubmed
,
Xenbase
Clare,
Voltage-gated sodium channels as therapeutic targets.
2000,
Pubmed
Cummins,
A novel persistent tetrodotoxin-resistant sodium current in SNS-null and wild-type small primary sensory neurons.
1999,
Pubmed
Eaholtz,
Restoration of inactivation and block of open sodium channels by an inactivation gate peptide.
1994,
Pubmed
Favre,
On the structural basis for ionic selectivity among Na+, K+, and Ca2+ in the voltage-gated sodium channel.
1996,
Pubmed
,
Xenbase
Featherstone,
Interaction between fast and slow inactivation in Skm1 sodium channels.
1996,
Pubmed
,
Xenbase
Featherstone,
A defect in skeletal muscle sodium channel deactivation exacerbates hyperexcitability in human paramyotonia congenita.
1998,
Pubmed
Geffeney,
Evolutionary diversification of TTX-resistant sodium channels in a predator-prey interaction.
2005,
Pubmed
,
Xenbase
Geffeney,
Mechanisms of adaptation in a predator-prey arms race: TTX-resistant sodium channels.
2002,
Pubmed
Gellens,
Primary structure and functional expression of the human cardiac tetrodotoxin-insensitive voltage-dependent sodium channel.
1992,
Pubmed
,
Xenbase
Hayward,
Slow inactivation differs among mutant Na channels associated with myotonia and periodic paralysis.
1997,
Pubmed
Hilber,
Selectivity filter residues contribute unequally to pore stabilization in voltage-gated sodium channels.
2005,
Pubmed
,
Xenbase
Hilber,
The selectivity filter of the voltage-gated sodium channel is involved in channel activation.
2001,
Pubmed
,
Xenbase
Hille,
The permeability of the sodium channel to organic cations in myelinated nerve.
1971,
Pubmed
Hille,
The permeability of the sodium channel to metal cations in myelinated nerve.
1972,
Pubmed
Horn,
Immobilizing the moving parts of voltage-gated ion channels.
2000,
Pubmed
Jayne,
SELECTION ON LOCOMOTOR PERFORMANCE CAPACITY IN A NATURAL POPULATION OF GARTER SNAKES.
1990,
Pubmed
Jost,
Toxin-resistant sodium channels: parallel adaptive evolution across a complete gene family.
2008,
Pubmed
Kaneko,
TTX resistivity of Na+ channel in newt retinal neuron.
1997,
Pubmed
Lipkind,
KcsA crystal structure as framework for a molecular model of the Na(+) channel pore.
2000,
Pubmed
Maruta,
Two critical residues in p-loop regions of puffer fish Na+ channels on TTX sensitivity.
2008,
Pubmed
Mitrovic,
Role of domain 4 in sodium channel slow inactivation.
2000,
Pubmed
Noda,
A single point mutation confers tetrodotoxin and saxitoxin insensitivity on the sodium channel II.
1989,
Pubmed
,
Xenbase
Ong,
A structural rearrangement in the sodium channel pore linked to slow inactivation and use dependence.
2000,
Pubmed
Pathak,
The cooperative voltage sensor motion that gates a potassium channel.
2005,
Pubmed
,
Xenbase
Penzotti,
Differences in saxitoxin and tetrodotoxin binding revealed by mutagenesis of the Na+ channel outer vestibule.
1998,
Pubmed
,
Xenbase
Pérez-García,
Structure of the sodium channel pore revealed by serial cysteine mutagenesis.
1996,
Pubmed
,
Xenbase
Pérez-García,
Mechanisms of sodium/calcium selectivity in sodium channels probed by cysteine mutagenesis and sulfhydryl modification.
1997,
Pubmed
,
Xenbase
Richmond,
Defective fast inactivation recovery and deactivation account for sodium channel myotonia in the I1160V mutant.
1997,
Pubmed
,
Xenbase
Ruben,
Steady-state availability of sodium channels. Interactions between activation and slow inactivation.
1992,
Pubmed
Ruben,
Holding potential affects the apparent voltage-sensitivity of sodium channel activation in crayfish giant axons.
1990,
Pubmed
Santarelli,
A cation-pi interaction discriminates among sodium channels that are either sensitive or resistant to tetrodotoxin block.
2007,
Pubmed
,
Xenbase
Satin,
A mutant of TTX-resistant cardiac sodium channels with TTX-sensitive properties.
1992,
Pubmed
,
Xenbase
Stefani,
Cut-open oocyte voltage-clamp technique.
1998,
Pubmed
,
Xenbase
Strausberg,
Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
2002,
Pubmed
Terlau,
Mapping the site of block by tetrodotoxin and saxitoxin of sodium channel II.
1991,
Pubmed
,
Xenbase
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
Tsushima,
Altered ionic selectivity of the sodium channel revealed by cysteine mutations within the pore.
1997,
Pubmed
,
Xenbase
Vedantham,
Rapid and slow voltage-dependent conformational changes in segment IVS6 of voltage-gated Na(+) channels.
2000,
Pubmed
,
Xenbase
Venkatesh,
Genetic basis of tetrodotoxin resistance in pufferfishes.
2005,
Pubmed
Vilin,
A single residue differentiates between human cardiac and skeletal muscle Na+ channel slow inactivation.
2001,
Pubmed
,
Xenbase
Wang,
Sequence and genomic structure of the human adult skeletal muscle sodium channel alpha subunit gene on 17q.
1992,
Pubmed
Xiong,
A conserved ring of charge in mammalian Na+ channels: a molecular regulator of the outer pore conformation during slow inactivation.
2006,
Pubmed
,
Xenbase
Yang,
The external pore loop interacts with S6 and S3-S4 linker in domain 4 to assume an essential role in gating control and anticonvulsant action in the Na(+) channel.
2009,
Pubmed
,
Xenbase
Yotsu-Yamashita,
Binding properties of (3)H-PbTx-3 and (3)H-saxitoxin to brain membranes and to skeletal muscle membranes of puffer fish Fugu pardalis and the primary structure of a voltage-gated Na(+) channel alpha-subunit (fMNa1) from skeletal muscle of F. pardalis.
2000,
Pubmed