Tarantula Toxin Locks Voltage-Gated Sodium Channels in Nerve Cells; Cryo-EM Study of Mechanism May Offer Clues to Treating Chronic Pain

Tararantulas may be unsightly and venomous, but surprisingly their hunter toxin may hold answers to better control of chronic pain. A bird-catching Chinese tarantula bite contains a stinger-like poison that plunges into a molecular target in the electrical signaling system of their prey's nerve cells. A new, high-resolution cryo-electron microscopy study shows how the stinger quickly locks the voltage sensors on sodium channels, the tiny pores on cell membranes that create electrical currents and generate signals to operate nerves and muscles. Trapped in their resting position, the voltage sensors are unable to activate. The findings were published online on November 23, 2020 in Molecular Cell, a journal of Cell Press. The article is titled “Structural Basis for High-Affinity Trapping of the NaV1.7 Channel in Its Resting State by Tarantula Toxin.” "The action of the toxin has to be immediate because the tarantula has to immobilize its prey before it takes off," said William Catterall, PhD, Professor and Chair of Pharmacology at the University of Washington School of Medicine. He was the senior researcher, along with Pharmacology Professor and Howard Hughes Medical Institute Investigator, Ning Zheng, PhD, on the study of the molecular damage inflicted by tarantula venom. While some might dismiss tarantulas as ugly, tough, and mean, medical scientists are actually interested in their venom's ability to trap the resting state of the voltage sensor on voltage-gated sodium channels and shut them down. Such studies of toxins from these "big, nasty dudes," as Dr. Catterall describes them, could point to new approaches to structurally designing drugs that might treat chronic pain by blocking sensory nerve signals. Dr. Catterall explained that chronic pain is a difficult-to-treat disorder.
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