title: Biophysical costs associated with tetrodotoxin resistance in the sodium channel pore of the garter snake, Thamnophis sirtalis.
abstract: 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 arms race, 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.
authors.affiliation: Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, BC, Canada. paull@sfu.ca
authors.forename: Chong Hyun
authors.initials: CH
authors.lastname: Lee
authors.forename: David K
authors.initials: DK
authors.lastname: Jones
authors.forename: Christopher
authors.initials: C
authors.lastname: Ahern
authors.forename: Maen F
authors.initials: MF
authors.lastname: Sarhan
authors.forename: Peter C
authors.initials: PC
authors.lastname: Ruben
mesh_terms: D000818:Animals; D055592:Biophysical Phenomena / Q000187:drug effects* / Q000235:genetics; D001703:Biophysics / Q000379:methods; D017812:Colubridae / Q000378:metabolism; D004558:Electric Stimulation / Q000379:methods; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects / Q000235:genetics; D008564:Membrane Potentials / Q000187:drug effects* / Q000235:genetics; D008845:Microinjections / Q000379:methods; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D062553:NAV1.4 Voltage-Gated Sodium Channel; D033661:Oocysts; D018408:Patch-Clamp Techniques / Q000379:methods; D026941:Sodium Channel Blockers / Q000737:chemistry / Q000494:pharmacology*; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism*; D013779:Tetrodotoxin / Q000737:chemistry / Q000494:pharmacology*; D014981:Xenopus
chemical_list: D009124:Muscle Proteins; D062553:NAV1.4 Voltage-Gated Sodium Channel; C106251:SCN4A protein, human; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D013779:Tetrodotoxin
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