Coral snake venom: Mode of action revealed


Coral snakes (Micrurus mipartitus) are non-aggressive and inhabit sparsely populated areas. Coral snakes have a powerful neurotoxin that paralyzes the breathing muscles. Mechanical or artificial respiration, along with large doses of anti-venom, are often required to save a victim’s life. There is usually only mild pain associated with a bite, but respiratory failure can occur within hours. The secret behind the lethality of coral snake venom has been unknown for a decade until a group of international scientists published their study online in the Proceedings of the National Academy of Sciences, the week of Feb. 9. Coral snake venom causes deadly seizures in prey while targeting unique proteins unlike most other snake venoms.

Biochemical studies showed that the active ingredient of the venom is actually a twin protein, dubbed micrurotoxins (MmTX) named after the coral snake Micrurus mipartitus. Most of the snake venoms act on specialized proteins, nicotinic acetylcholine receptors on the surface of nerve cells that make muscles contract paralyzing the victim. MmTX was shown to cause a repeating pattern of relaxation and seizures in mice however MmTX had no effect on cells saturated with nicotinic acetylcholine receptors tested invitro suggesting a different target for MmTX. Using radioactive labeled protein, researchers could identify MmTX binding to GABA(A) receptors on nerve cells in the brain and spinal cord. These GABA(A) receptors allow the influx of negatively charged chloride ions in response to GABA molecules in a nerve cell that has just fired a pulse or signal and aids to reset the cells equilibrium making it ready for the next signal. The MmTX in the snake venom binds to the GABA(A) receptors 100 times tighter than any other compounds like diazepam and alprazolam used as anti-anxiety medications. This tight binding changes the receptor’s shape, making it far too sensitive to GABA. GABA molecules when bind to these receptors allow the pores to remain open and the nerve cell is never able to reset, causing it to misfire, convulsing the animal and potentially causing death. The research team aims to use MmTX as a tool to understand more about these receptors that play critical roles in epilepsy, schizophrenia, chronic pain and other disorders

Researchers involved in this study include Jean-Pierre Rosso, Brigitte Ceard and Pierre Bougis of Aix Marseille University in France; Jurgen Schwarz and Matthias Kneussel of the University Medical Center Hamburg-Eppendorf in Germany; Marcelo Diaz-Bustamante of The Johns Hopkins University; Maria Gutierrex of the Universidad de Costa Rica; and Olaf Pongs of the Universitat des Saarlandes in Germany.


The original publication can be accessed here.