The Janus-faced atracotoxins are specific blockers of invertebrate K<inf>Ca</inf>channels

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Journal Article
FEBS Journal, 2008, 275 (16), pp. 4045 - 4059
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The Janus-faced atracotoxins are a unique family of excitatory peptide toxins that contain a rare vicinal disulfide bridge. Although lethal to a wide range of invertebrates, their molecular target has remained enigmatic for almost a decade. We demonstrate here that these toxins are selective, high-affinity blockers of invertebrate Ca2+-activated K+(KCa) channels. Janus-faced atracotoxin (J-ACTX)-Hv1c, the prototypic member of this toxin family, selectively blocked KCachannels in cockroach unpaired dorsal median neurons with an IC50of 2 nm, but it did not significantly affect a wide range of other voltage-activated K+, Ca2+or Na+channel subtypes. J-ACTX-Hv1c blocked heterologously expressed cockroach large-conductance Ca2+-activated K+(pSlo) channels without a significant shift in the voltage dependence of activation. However, the block was voltage-dependent, indicating that the toxin probably acts as a pore blocker rather than a gating modifier. The molecular basis of the insect selectivity of J-ACTX-Hv1c was established by its failure to significantly inhibit mouse mSlo currents (IC50∼ 10 μm) and its lack of activity on rat dorsal root ganglion neuron KCachannel currents. This study establishes the Janus-faced atracotoxins as valuable tools for the study of invertebrate KCachannels and suggests that KCachannels might be potential insecticide targets. © 2008 The Authors.
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