Animals use their sensory and motor systems to navigate their environment and to mediate interactions with other animals. Ion channels expressed in excitable membranes are critical for encoding information about and producing responses to environmental stimuli. Given the critical role of ion channels in transmitting neuronal signals and producing muscle contractions, it is not surprising that some animals have evolved toxins that bind ion channels and disrupt their activity. Toxin producers use their chemical weapons to subdue their prey and to deter predators. Toxins that induce pain, paralysis, seizures and death may impose strong selection on the receiver, potentially driving the evolution of adaptations that mediate interactions between toxin producers and their enemies.

My goal is to understand how receivers respond to these selection pressures. Specifically, I want to determine the effects of toxins on the structure and function of ion channels expressed in the nerve and muscle tissue of receivers, and, ultimately, understand how changes in channels feed back on and influence predatory, foraging and feeding behavior in the receiver. Bark scorpions (Centruroides spp.) produce toxins that selectively bind sodium- (Na+) and potassium- (K+) ion channels expressed in peripheral pain-pathway neurons (nociceptors) and skeletal-muscle fibers. Bark scorpion venom induces intense pain, uncontrolled muscle contractions and respiratory failure in sensitive mammals. Grasshopper mice (Onychomys spp.), predators of bark scorpions, have evolved resistance to their venom. Physiological assays demonstrated that grasshopper mice’s skeletal muscle is insensitive to bark scorpion toxins. Recordings of Na+ current from channels expressed in grasshopper mice’s nociceptors revealed a novel mechanism where a component of bark scorpion venom is co-opted by these Na+ channels – to block the very pain signals that the toxins are generating. Cloning and sequencing of genes that encode the muscle and nociceptor Na+ channels from grasshopper mice revealed structural modifications in both channel subtypes that are positioned to either inhibit or co-opt toxin activity. Current work is focused on using mutagenesis, expression and electrophysiology to determine how structural modifications of grasshopper mice Na+ channels produce functional changes in skeletal muscle and nociceptors that explain insensitivity to bark scorpion venom.