In a finding that promises new research into pain management, a tarantula toxin molecule has been revealed to use a “stinger” to permanently close the voltage sensors on nerve cells’ sodium channels.
Chronic pain is difficult to treat, and attempts to seek relief can sometimes lead to opiate overdose, addiction, prolonged withdrawal, and even death. This means that there is a critical need to develop pain management medications that are safer, more effective and non-addictive. Tarantula toxin is of interest because it has to be fast-acting, shutting down the nerves of the tarantula’s prey and immobilising it before it can escape.
The tarantula toxin’s mechanism of action has proved elusive: the tarantula toxin-ion channel chemical complex has been hard to capture in its functional form. This has made it especially challenging to replicate the calcium-channel blocking effect in a small molecular form suitable for anaesthetic compounds. To overcome this obstacle, the researchers took a toxin-binding region from a specific type of human sodium channel that is key to pain transmission and imported it into their bacterium-derived model ancestral sodium channel. In doing so, they successfully obtained a clear molecular view of the configuration of the potent toxin from tarantula venom as it tightly binds to the sodium channel receptor site.
Prof William Catterall of the University of Washington School of Medicine explains: “Remarkably, the toxin plunges a ‘stinger’ lysine residue into a cluster of negative charges in the voltage sensor to lock it in place and prevent its function. Related toxins from a wide range of spiders and other arthropod species use this molecular mechanism to immobilise and kill their prey.”
The researchers hope that these insights will lead to the development of a new variety of anaesthetic compounds.
Source: News-Medical.Net
