Crotamine inhibits preferentially fast-twitching muscles but is inactive on sodium channels

Carina T. Rizzi, João Luís Carvalho-de-Souza, Emanuele Schiavon, Antônio Carlos Cassola, Enzo Wanke, Lanfranco R.P. Troncone

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

Crotamine is a peptide toxin from the venom of the rattlesnake Crotalus durissus terrificus that induces a typical hind-limb paralysis of unknown nature. Hind limbs have a predominance of fast-twitching muscles that bear a higher density of sodium channels believed until now to be the primary target of crotamine. Hypothetically, this makes these muscles more sensitive to crotamine and would explain such hind-limb paralysis. To challenge this hypothesis, we performed concentration vs. response curves on fast (extensor digitorum longus (EDL)) and slow (soleus) muscles of adult male rats. Crotamine was tested on various human Na+ channel isoforms (Nav1.1-Nav1.6 α-subunits) expressed in HEK293 cells in patch-clamp experiments, as well as in acutely dissociated dorsal root ganglion (DRG) neurons. Also, the behavioral effects of crotamine intoxication were compared with those of a muscle-selective sodium channel antagonist μ-CgTx-GIIIA, and other sodium-acting toxins such as tetrodotoxin α- and β-pompilidotoxins, sea anemone toxin BcIII, spider toxin Tx2-6. Results pointed out that EDL was more susceptible to crotamine than soleus under direct electrical stimulation. Surprisingly, electrophysiological experiments in human Nav1.1 to Nav1.6 Na+ channels failed to show any significant change in channel characteristics, in a clear contrast with former studies. DRG neurons did not respond to crotamine. The behavioral effects of the toxins were described in detail and showed remarkable differences. We conclude that, although differences in the physiology of fast and slow muscles may cause the typical crotamine syndrome, sodium channels are not the primary target of crotamine and therefore, the real mechanism of action of this toxin is still unknown.

Original languageEnglish (US)
Pages (from-to)553-562
Number of pages10
JournalToxicon
Volume50
Issue number4
DOIs
StatePublished - Sep 15 2007
Externally publishedYes

Keywords

  • Behavior
  • Crotalus durissus terrificus
  • Crotamine
  • Muscle
  • Sodium channels
  • Toxin

ASJC Scopus subject areas

  • Toxicology

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