Adaptive Tetrodotoxin-Resistance in Garter Snake Sodium Channels

Tetrodotoxin (TTX) is a neurotoxin 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. 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. We tested the properties of NaV with TTX resistance found in garter snake populations. We observed some surprising changes in gating properties and ion selectivity of the TTX resistant NaV. These results suggest TTX resistance comes at a cost to performance caused by changes in the biophysical properties and/or ion selectivity of the TTX resistant