α-Dendrotoxin inhibits the ASIC current in dorsal root ganglion neurons from rat

  • Neurosci Lett. 2015 Oct 8:606:42-7. doi: 10.1016/j.neulet.2015.08.034.
Adriana Báez  1 Emilio Salceda  2 Martín Fló  3 Martín Graña  4 Cecilia Fernández  5 Rosario Vega  6 Enrique Soto  7
Affiliations
  • 1. Instituto de Fisiología, Benemérita Universidad Autónoma de Puebla (BUAP), 14 sur 6301, CU, San Manuel, Puebla, Pue., CP 72570, Mexico. Electronic address: [email protected].
  • 2. Instituto de Fisiología, Benemérita Universidad Autónoma de Puebla (BUAP), 14 sur 6301, CU, San Manuel, Puebla, Pue., CP 72570, Mexico. Electronic address: [email protected].
  • 3. Faculty of Chemistry, UDELAR, Av. Gral., Flores, Montevideo 2124, Uruguay. Electronic address: [email protected].
  • 4. Institut Pasteur de Montevideo, Mataojo 2020, Montevideo 11400, Uruguay. Electronic address: [email protected].
  • 5. Faculty of Chemistry, UDELAR, Av. Gral., Flores, Montevideo 2124, Uruguay. Electronic address: [email protected].
  • 6. Instituto de Fisiología, Benemérita Universidad Autónoma de Puebla (BUAP), 14 sur 6301, CU, San Manuel, Puebla, Pue., CP 72570, Mexico. Electronic address: [email protected].
  • 7. Instituto de Fisiología, Benemérita Universidad Autónoma de Puebla (BUAP), 14 sur 6301, CU, San Manuel, Puebla, Pue., CP 72570, Mexico. Electronic address: [email protected].
Abstract

Dendrotoxins are a group of peptide toxins purified from the venom of several mamba snakes. α-Dendrotoxin (α-DTx, from the Eastern green mamba Dendroaspis angusticeps) is a well-known blocker of voltage-gated K(+) channels and specifically of K(v)1.1, K(v)1.2 and K(v)1.6. In this work we show that α-DTx inhibited the ASIC currents in DRG neurons (IC50=0.8 μM) when continuously perfused during 25 s (including a 5 s pulse to pH 6.1), but not when co-applied with the pH drop. Additionally, we show that α-DTx abolished a transient component of the outward current that, in some experiments, appeared immediately after the end of the acid pulse. Our data indicate that α-DTx inhibits ASICs in the high nM range while some Kv are inhibited in the low nM range. The α-DTx selectivity and its potential interaction with ASICs should be taken in consideration when DTx is used in the high nM range.

Keywords
APETx2; ASIC; K(Na); K(v); Kunitz domain; Proton gated; Slack; Slick.
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