National Geographic

This Mouse Turns Agonising Scorpion Venom Into A Painkiller

Move aside, honey badger. There’s a new contender for the most badass mammal: the southern grasshopper mouse. This little creature from the south-western USA attacks and eats bark scorpions—a group of large arachnids, whose stings are incredibly painful and often fatal. When humans get stung, they say the pain’s like having a cigarette stubbed out on your skin, followed by hours of throbbing. The toxins should easily be powerful enough to kill a small rodent.

But the grasshopper mouse doesn’t care.

It viciously attacks and eats bark scorpions. When it gets stung—and it gets stung a lot—it barely seems to notice. Ashlee Rowe from Michigan State University (and formerly the University of Texas at Austin) has discovered how it copes.

The mouse is armed with a protein that stops its nerves from firing whenever it recognises the toxins in a bark scorpion’s venom. This doesn’t just stop the venom from triggering intense pain; it means that the scorpion’s venom actually prevents pain! The southern grasshopper mouse turns a scorpion’s sting from a painful killer into a painkiller.

“It’s like an evolutionary martial art,” says Rowe. “The mouse is using the scorpion’s strength against it.”

The bark scorpion’s venom works by attaching to a protein called Nav1.7, which is found on the surface of pain-sensing nerve cells. The protein acts like a doorway and the venom forces it open, allowing sodium ions to flood into the nerve and causing it to fire. Nav1.7 is very similar across different mammals, which is why a bark scorpion’s venom is equally effective at causing pain in humans as in rodents.

At first, Rowe guessed that the grasshopper mouse must have mutations in Nav1.7 that change its shape, so that the venom can’t recognise it any more. That’s the usual way in which animals evolve resistance to otherwise deadly toxins.

But she was wrong—the grasshopper mouse’s version of Nav1.7 opens in the presence of scorpion venom as readily as that of any other rodent. Instead, its secret lies in a second protein called Nav1.8. This one sits in the same neurons in Nav1.7, and it’s responsible for maintaining the pain signals that its counterpart initiates. Rather than tweaking Nav1.7 to ignore scorpion venom, the mouse has tweaked Nav1.8 to recognise it.

By reconstructing Nav1.8 in the lab, Rowe’s team found that scorpion venom has no effect on the house mouse version, but readily sticks to the grasshopper mouse’s one… and blocks it. This immediately kills any pain signals that are initiated by Nav1.7.

“That’s what is so cool about this paper,” says Michael Nitabach from Yale University, who studies similar proteins. “The evasion mechanism is based on the accumulation of mutations in a second, distinct sodium channel in the pain-sensing neurons of the mouse.”

And by blocking Nav1.8, the venom also dulls the signals caused by other painful stimuli too. When the team injected small doses of irritants into the paws of mice, they saw that the grasshopper mouse was more bothered by an injection of saline than one of scorpion venom! And when they injected formaldehyde into a grasshopper mouse’s paw, the rodents were less bothered after a dose of scorpion venom.

Southern grasshopper mouse takes out a scorpion. Credit: Matthew and Ashlee Rowe

Southern grasshopper mouse takes out a scorpion. Credit: Matthew and Ashlee Rowe

The team then sequenced the gene that encodes Nav1.8 in both mouse species, and discovered that the differences between them boil down to just two amino acids, out of hundreds. In the house mouse, the 859th amino acid in Nav1.8 is a glutamic acid, while the 862nd one is a glutamine. In the grasshopper mouse, they’re reversed. That’s it. That swap is enough to make Nav1.8 respond to a scorpion’s venom, and to make a rodent impervious to its sting.

There’s an interesting parallel to this evolutionary story in a bizarre African rodent called the naked mole rat. They’re not threatened by bark scorpions, but they do face chokingly high levels of carbon dioxide in their underground colonies. This acidic gas increases the levels of protons in their blood, which triggers acid sensors in their neurons. That would normally cause pain, but the naked mole rat’s version of Nav1.7 also recognises protons, and shuts down in their presence. And that makes the animal insensitive to acids.

Both Nav1.7 and Nav1.8 are very similar across a lot of different species, but small changes can clearly have profound effects. They allow the naked mole rat to live underground, and they allow the grasshopper mouse to feast upon well-defended prey.

But what about the scorpions? Surely they would eventually evolve a way around the mouse’s impunity. Rowe suspects that this might be happening. “I’ve begun to look at population differences in the scorpions,” she says. “There are some populations that are a little more toxic than others, and they tend to the be the ones that co-exist with the grasshopper mouse. I haven’t looked at pain levels yet, but there might be some sort of arms race.”

Reference: Rowe, Xiao, Rowe, Cummins & Zakon. 2013. Voltage-Gated Sodium Channel in Grasshopper Mice Defends Against Bark Scorpion Toxin. Science http://dx.doi.org/10.1126/science.1236451

There are 10 Comments. Add Yours.

  1. jules
    October 25, 2013

    How does the mouse neutralise the poisonousness of the venom? You explained that it doesn’t feel any pain, but pain and poison are not the same thing. …some poisons, like carbon monoxide, for example, are painless…

    [Good question. The short answer is that we don't know but Rowe is looking into it. - Ed]

  2. kit
    October 25, 2013

    That explains the lack of pain, yet how do the mice deal with the toxins that are normally fatal i.e. how is it able to eat the scorpions containing the toxins?

  3. Hypnotosov
    October 25, 2013

    Causing pain is the primary mechanism of the venom, the other symptoms are side-effects of triggering the pain receptors. So if these are inhibited by the Nav1.8 protein that renders the venom ineffective.
    The scorpion itself doesn’t appear to be poisonous, so you could probably eat it after cutting out the venom gland (don’t do this without supervision from an expert).

    • jules
      October 25, 2013

      The how does the venom kills things (ie other mice that can’t neutralise it)? They die of pain?!?

  4. Stephen Mackenzie
    October 25, 2013

    Protons? Really? How? Or a typo for proteins?

  5. Hypnotosov
    October 25, 2013

    I may have been a bit hasty in my comments based on most sites mentioning only pain and local numbness/tingling sensation as symptoms. But it seems the scorpion’s venom has more obvious neurotoxic effects:
    “utonomic symptoms include hypertension, tachycardia, diaphoresis, emesis, and bronchoconstriction. The somatic motor symptoms reported include ataxia, muscular fasciculations, restlessness, thrashing, and opsoclonus”

    http://toxnet.nlm.nih.gov/cgi-bin/sis/search/a?dbs+hsdb:@term+@DOCNO+8064

  6. diane
    October 25, 2013

    Stephen–I thought the same thing on first reading, but it’s accurate as written. By definition, an increase in acidity is an increase in proton (AKA hydrogen ion) concentration.

    Ed–wonderful write-up, but then, that’s no surprise and why I come here!

  7. psweet
    October 25, 2013

    If the effects are all neurotoxic, then a protein that prevents nerves from firing might neutralize all of them, right? (At least, if they work by inducing firing.

    Also, a compound that is toxic if delivered subcutaneously isn’t always a problem if eaten. If the digestive system can break the compound down before it’s absorbed, it isn’t as much of an issue. That’s why most vaccines aren’t delivered orally.

  8. robin
    October 28, 2013

    Protons, Stephen. Protons without stable attachments are what make something acidic. Not proteins.

  9. Tristan Henry
    October 28, 2013

    @Stephen Mackenzie
    Yes, protons. Its a simplified way to say H+ concentration, the stuff that causes acidity. When something has a low(acidic) pH it has a high concentration of H+ ions. An H+ ion is a hydrogen atom with no electron, essentially, a proton.

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