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

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 Kv1.1, Kv1.2 and Kv1.6. In this work we show that α-DTx inhibited the ASIC currents in DRG neurons (IC50=0.8μM) when continuously perfused during 25s (including a 5s 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.