Rare Seizure Inducing Snake Venom Finally Decoded

For more than a decade, a vial of rare snake venom has been sitting in a lab while scientists stared it down, scratching their heads in wonder. Understanding how exactly a toxin works is a very important step in creating an antivenin (antivenom) for snake bites. However, in the case of rare coral snakes, how it caused severe seizures in its victims had remained an utter mystery, until now.

According to a study recently published in the journal Proceedings of the National Academy of Sciences (PNAS), researchers from five universities and medical facilities pooled efforts to determine how the venom of the rare coral snake Micrurus mipartitus incapacitates its victims, once and for all.

"What we found are the first known animal toxins, and by far the most potent compounds, to target GABA(A) receptors," Frank Bosmans, at the Johns Hopkins University School of Medicine, explained in a statement. "Once they bind to the receptors, they don't let go."

What Bosmans is talking about is the function of the venom's active ingredient - a rare twin protein dubbed "micrurotoxins" (MmTX) that was identified after years of biochemical testing. In most types of snake venom, viscous protein pairs like these will infiltrate a body to bind to a victim's nerve cells. This will in turn trigger an automatic response for muscles to contract, paralyzing the victim and potentially even stopping the heart.

However, when the research team tested MmTX on lab-grown nerve cells, the didn't see this usual type of reaction. That was strange because experts are nearly certain that M. mipartitus does impact the nervous system, triggering a looping pattern of relaxation and seizures - similar to what's seen in epilepsy - in mice. (Scroll to read on...)

To determine what was really going on, the team then tagged the MmTX pair specifically with a radioactive marker. This allowed them to directly trace what the active ingredient was up to.

They determined that the proteins were actually binding to pores on nerve cells in the brain and spinal cord called GABA(A) receptors. These receptors normally have only one job: to reset a nerve after it fires a signal.

What they found was that the MmTX were actually tightly lodging themselves into these pores after they opened. Unable to close at all, the nerve cell is never able to reset, causing it to misfire, convulsing the victim and potentially causing death.

Bosmans noted that this was unexpected, because interfering with GABA(A) receptors is commonly used in modern medicine as a form of helpful therapy.

"Anti-anxiety medications like diazepam and alprazolam bind to GABA(A) receptors too, but they cause relaxation instead of seizures because they bind much more loosely," he explained.

What makes this toxin different then is how violently and tightly it lodges itself into the pore, preventing any closing action at all.

Since errors in GABA(A) receptors can cause epilepsy, schizophrenia and chronic pain, the team now hopes that further work with the venom could shed light on the mechanisms of these and other disorders.

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