Veratridine: A Janus-Faced Modulator of Voltage-Gated Sodium Ion Channels

Robert A. Craig, Catherine E. Garrison, Phuong T. Nguyen, Vladimir Yarov-Yarovoy, J. Du Bois

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Voltage-gated sodium ion channels (NaVs) are integral to both neuronal and muscular signaling and are a primary target for a number of proteinaceous and small molecule toxins. Included among these neurotoxins is veratridine (VTD), a C-nor-D homosteroidal alkaloid from the seeds of members of the Veratrum genus. VTD binds to NaV within the pore region, causing a hyperpolarizing shift in the activation threshold in addition to reducing peak current. We have characterized the activity of VTD against heterologously expressed rat NaV1.4 and have demonstrated that VTD acts on the channel as either an agonist or antagonist depending on the nature of the electrophysiological stimulation protocol. Structure-activity studies with VTD and VTD derivatives against NaV mutants show that the functional duality of VTD can be decoupled. These findings suggest that the dichotomous activity of VTD may derive from two distinct, use-dependent binding orientations of the toxin.

Original languageEnglish (US)
Pages (from-to)418-426
Number of pages9
JournalACS Chemical Neuroscience
Issue number3
StatePublished - Feb 5 2020


  • electrophysiology
  • Site II
  • Sodium channel
  • veratridine

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Cognitive Neuroscience
  • Cell Biology


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