The Conopeptide αD-FrXXA, an Inhibitor of Voltage-Gated Potassium Channels

The conopeptide αD-FrXXA was previously isolated by our team from the venom of the vermivorous snail Conus fergusoni. This toxin is composed of two chains of 47 amino acids and inhibits neuronal and muscular subtypes of nAChR. In this study, we explored its effects on voltage-gated potassium channels heterologously expressed in Xenopus laevis oocytes using the two-electrode voltage-clamp technique (TEVC). At a concentration of 15 μM, αD-FrXXA was able to inhibit by 50% or more the currents of four subtypes of the Kv1 subfamily and slightly inhibit (<20%) two subtypes of the EAG subfamily. The conopeptide αD-FrXXA inhibits in a concentration-dependent manner the subtypes Kv1.3 (IC₅₀ 0.38 ± 0.06 μM) and Kv1.6 (IC₅₀ 0.52 ± 0.14 μM). The results reported here are noteworthy because this α-conopeptide behaves similarly to the α/κJ-PlXIVA conopeptide that inhibits nAChR and Kv channels.