The first Kunitz-type proteins from a viperid venom that potentiate neuromuscular transmission

Abstract

Kunitz-type proteins that interfere with neuronal transmission have been thus far exclusively detected in venoms of elapid snakes. Here, we report for the first time that such proteins are also present in the venom of a viperid snake. From the venom of the nose-horned viper (Vipera ammodytes ammodytes; Vaa), we isolated Kunitz-type chymotrypsin inhibitors (VaaChi) and demonstrated that these molecules also significantly increase the amplitudes of an indirectly evoked simple muscle contraction of the mouse hemidiaphragm, the end-plate potential and the miniature end-plate potential. By facilitating neuromuscular transmission, these proteins resemble structurally homologous dendrotoxins from mamba (Dendroaspis spp.) venoms, which are blockers of voltage-dependent K⁺ channels at the presynaptic site of the neuromuscular junction. What is the mechanism behind facilitation of neuromuscular transmission by VaaChi has not been established yet, however, blocking of K⁺ channels does not seem to be the most probable option.

Keywords: Chymotrypsin inhibitor; Dendrotoxin; Facilitation; K(+) channel inhibitor; Kunitz-type protein; Neuromuscular transmission; Venom; Viperidae.