Meeting Abstract
The interaction between toxic newts (Taricha) and resistant garter snakes (Thamnophis) is a model system of predator-prey coevolution. Pacific newts defend themselves with the potent neurotoxin, tetrodotoxin (TTX). TTX specifically binds to the outer pore of voltage-gated sodium channels, NaV proteins. These proteins are responsible for the first electrical event initiating every action potential and every skeletal and cardiac muscle contraction. TTX-ligation to the channel pore prevents sodium ion movement through the membrane, thereby abolishing excitability, and leading to numbness, paralysis, and eventually death by respiratory arrest. TTX serves as an agent of selection on at least three species of Thamnophis that prey on sympatric Taricha. Thamnophis atratus, couchii, and sirtalis have independently evolved adaptive mutations within the pore of the skeletal muscle channel variant, NaV1.4. The amino acid substitutions reduce the affinity of TTX to the pore, thereby providing physiological resistance to TTX. Here, we discuss how these same mutations may actually reduce sodium channel performance. We show that animals carrying these mutations display diminished skeletal muscle performance. This hypofunction is likely explained by alterations to biophysical properties of the channel, such as the sodium-selectivity or total sodium current through the membrane. We investigate channel hypofunction through site-directed mutagenesis, constructing the naturally occurring TTX-resistant mutations and contrasting these to a TTX-sensitive template. We then assess the behavior of mutant sodium channels by patch clamp electrophysiology to reveal interesting support for this biophysical tradeoff.
