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Learning from scorpions to control impulses

Date:
January 26, 2015
Source:
The Rockefeller University Press
Summary:
Scorpions can teach us a lot about the benefits of prolonging nerve impulses, and we might now be better students. The results of a new study could pave the way for easier identification of drugs that function similarly to scorpion venom, but with happier results for the recipient.
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This is a depiction of the interaction of scorpion venom with the isolated "paddle" region of a Nav channel domain bound to a sensor chip.
Credit: Kate Baldwin (http://www.k8baldwin.com)

Scorpions can teach us a lot about the benefits of prolonging nerve impulses, and we might now be better students thanks to a study published in The Journal of General Physiology. The results could pave the way for easier identification of drugs that function similarly to scorpion venom, but with happier results for the recipient.

For venomous animals seeking to cripple their prey or defend against predators, voltage-gated sodium (Nav) channels are attractive targets. These transmembrane proteins, which play a key role in the generation of electrical signals in neurons, consist of four domains that make up the regions that sense changes in membrane voltage as well as the pore through which sodium ions can cross the membrane. Various animal toxins bind to each domain's "paddle" region, a part of the voltage-sensing domain, so named for the shape created by the helix-turn-helix structure.

Animal toxins can affect Nav channel function differently based on which paddle they target. Some toxins, that bind to paddles in voltage-sensing domains I to III, for instance, disrupt channel activation to inhibit the propagation of nerve impulses. Certain scorpion toxins, on the other hand, which bind to the paddle in domain IV, prolong nerve impulses by inhibiting channel inactivation. Finding molecules that similarly target the paddle could therefore be useful in developing drugs that correct abnormal channel activity. But techniques to identify such compounds can be time consuming and tedious, requiring expression of the full-length channel.

In the new study, a team of researchers from Aix Marseille Université in France and Johns Hopkins Medicine in Baltimore, Maryland, isolated the domain IV paddle and found that, even when bound to a chip, it remained sensitive to scorpion venom. The results indicate that the isolated paddle could be used to identify other molecules that target this pharmacologically important region, providing a much faster approach. The technique might also be used with other domain paddles to discover molecules that beneficially modify Nav channel activity.


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Materials provided by The Rockefeller University Press. Note: Content may be edited for style and length.


Journal Reference:

  1. M.-F. Martin-Eauclaire, G. Ferracci, F. Bosmans, P. E. Bougis. A surface plasmon resonance approach to monitor toxin interactions with an isolated voltage-gated sodium channel paddle motif. The Journal of General Physiology, 2015; 145 (2): 155 DOI: 10.1085/jgp.201411268

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The Rockefeller University Press. "Learning from scorpions to control impulses." ScienceDaily. ScienceDaily, 26 January 2015. <www.sciencedaily.com/releases/2015/01/150126095325.htm>.
The Rockefeller University Press. (2015, January 26). Learning from scorpions to control impulses. ScienceDaily. Retrieved May 23, 2017 from www.sciencedaily.com/releases/2015/01/150126095325.htm
The Rockefeller University Press. "Learning from scorpions to control impulses." ScienceDaily. www.sciencedaily.com/releases/2015/01/150126095325.htm (accessed May 23, 2017).

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