Secretive coral snakes are known for having the second-strongest venom of any snake, after the extremely deadly black mamba which you may remember from an iconic scene in the movie Kill Bill Vol. 2. These brightly colored snakes possess powerful neurotoxins that can rapidly paralyze its unlucky victims, causing them to die from respiratory failure. Fortunately for us, deaths are rare because their weak fangs and small mouths make it difficult for them to puncture human skin.
While it’s known what the venom of coral snakes is capable of, precisely how the toxins in the deadly juice of one particular coral snake species act on the nervous system has continued to elude scientists for many years. Now, after finally unraveling the venom’s potent recipe, researchers have managed to reveal how it causes victims to meet their demise.
Interestingly, it turns out that this venom contains the only known animal toxins to act in this particular fashion, tightly binding to the most common receptor found in the mammalian nervous system, the so called GABAA receptors. This causes an increase in spontaneous activity in the brains of victims, triggering deadly seizures.
Many toxins present in snake venoms paralyze victims by sticking to receptors at the junctions between nerve endings and muscles, which normally signal for the muscle to contract. But scientists soon realized that this wasn’t the case for the rare redtail coral snake, since dumping the toxins from its venom onto cells possessing an excess of these receptors didn’t appear to do anything. This was perplexing given that the toxins seem to cause bouts of relaxation and seizures, similar to epilepsy in mice.
To find out more, scientists from Aix Marseille University attached a radioactive label to the toxins, which allowed the researchers to identify which particular cellular proteins they bind to. As described in PNAS, this revealed that they stick to a common receptor found throughout the nervous system, the GABAA receptor, to which a widely distributed chemical messenger—GABA—normally binds.
GABA is an inhibitory neurotransmitter, meaning that it reduces the activity of the cells it attaches to, preventing excessive excitation and subsequent cellular damage that can occur as a result of this. When GABA binds to GABAA, the receptor opens up and allows negatively charged chloride ions to flow into the cell, which decreases its excitability.
The researchers found that when the toxins bound to the receptor, they triggered a conformational change which increased its susceptibility to GABA. Consequently, the receptor is left permanently opened, meaning neurons become excessively excited. This increase in neuronal activity results in intense seizures in prey, which can be fatal.
Alongside solving a long-standing mystery, scientists hope that these results could have further uses. For example, scientists could use these toxins to trigger seizures in assays that are designed to test out anti-epileptic drugs. Furthermore, it may be possible to use these molecules to help design therapeutics that modulate the activity of GABAA receptors, which are known to be involved in a variety of conditions, such as chronic pain.
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