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Inhibition of voltage‐gated Na + currents in sensory neurones by the sea anemone toxin APETx2
Author(s) -
Blanchard Maxime G,
Rash Lachlan D,
Kellenberger Stephan
Publication year - 2012
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.2011.01674.x
Subject(s) - biophysics , sea anemone , dorsal root ganglion , patch clamp , reversal potential , tetrodotoxin , xenopus , electrophysiology , ion channel , sodium channel , chemistry , voltage clamp , biology , membrane potential , microbiology and biotechnology , neuroscience , biochemistry , sensory system , sodium , receptor , ecology , organic chemistry , gene
BACKGROUND AND PURPOSE APETx2, a toxin from the sea anemone Anthropleura elegantissima , inhibits acid‐sensing ion channel 3 (ASIC3)‐containing homo‐ and heterotrimeric channels with IC 50 values < 100 nM and 0.1–2 µM respectively. ASIC3 channels mediate acute acid‐induced and inflammatory pain response and APETx2 has been used as a selective pharmacological tool in animal studies. Toxins from sea anemones also modulate voltage‐gated Na + channel (Na v ) function. Here we tested the effects of APETx2 on Na v function in sensory neurones. EXPERIMENTAL APPROACH Effects of APETx2 on Na v function were studied in rat dorsal root ganglion (DRG) neurones by whole‐cell patch clamp. KEY RESULTS APETx2 inhibited the tetrodotoxin (TTX)‐resistant Na v 1.8 currents of DRG neurones (IC 50 , 2.6 µM). TTX‐sensitive currents were less inhibited. The inhibition of Na v 1.8 currents was due to a rightward shift in the voltage dependence of activation and a reduction of the maximal macroscopic conductance. The inhibition of Na v 1.8 currents by APETx2 was confirmed with cloned channels expressed in Xenopus oocytes. In current‐clamp experiments in DRG neurones, the number of action potentials induced by injection of a current ramp was reduced by APETx2. CONCLUSIONS AND IMPLICATIONS APETx2 inhibited Na v 1.8 channels, in addition to ASIC3 channels, at concentrations used in in vivo studies. The limited specificity of this toxin should be taken into account when using APETx2 as a pharmacological tool. Its dual action will be an advantage for the use of APETx2 or its derivatives as analgesic drugs.