APETx2, Anthopleura elegantissima, Recombinant, E. coli

Primary Target
ASIC3

Reversible: yes

Toxicity: Standard Handling (A)

Originally isolated from sea anemone Anthopleura elegantissima, the 42 amino-acid toxin APETx2 is shown to block acidification-induced activation of homotrimeric acid-sensing ion channel composed of rat or human ASIC3 (IC₅₀ against pH 7.4 to 6 ramping-induced transient current = 63 nM and 175 nM by whole-cell patch-clamp using COS cells expressing respective channel), but not rat ASIC1a, ASIC1b, or ASIC2a, in a reversible manner, presumably via its N-terminus interaction with type I β turn that connects β-strands I&II in the ASIC3 extracellular β-ball region. In addition to acidification-induced classical transient current, APETx2 is also shown to inhibit the Na⁺-dependent, alkalization-induced nonconventional channel activity seen in human, but not rat, ASIC3 (complete inhibition by 1 µM APETx3; pH 8.0). APETx2 in vivo efficacy is demonstrated in various rat pain induction models, including acid- (via calf i.m. injection of 100 µL pH 4.0 saline on day 1&5) induced mechanical hypersensitivity (pain withdrawal threshold = 76% and 24% of control rats with or without 100 µL 2.2 µM APETx2 i.m. injection prior to the second pH 4.0 saline injection). Although structurally related to known K⁺ channel modulators APETx1 and BDS-1/II, APETx2 is reported to display much reduced potency against Kv3.4 (38% inhibition by 3 µM APETx2) and little or no effect toward hERG, Kv2.2, Kv3.1, Kv4.2, or Kv4.3 channel activity.

Delaunay, A., et al. 2012. Proc. Natl. Acad. Sci.109, 13124.
Sherwood, T.W., et al. 2012. Am. J. Physiol. Cell Physiol.303, C699.
Karczewski, J., et al. 2010. Br J Pharmacol.161, 950.
Chagot, B., et al. 2005. Protein Sci.14, 2003.

Diochot, S., et al. 2004. EMBO J.23, 1516.

H-Gly-Thr-Ala-Cys⁴-Ser-Cys⁶-Gly-Asn-Ser-Lys-Gly-Ile-Tyr-Trp-Phe-Tyr-Arg-Pro-Ser-Cys²⁰-Pro-Thr-Asp-Arg-Gly-Tyr-Thr-Gly-Ser-Cys³⁰-Arg-Tyr-Phe-Leu-Gly-Thr-Cys³⁷-Cys³⁸-Thr-Pro-Ala-Asp-OH (disulfide bonds: 4 → 37, 6 → 30, 20 → 38)

Supplied as a trifluoroacetate salt.

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.

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