The facilitatory actions of snake venom phospholipase A(2) neurotoxins at the neuromuscular junction are not mediated through voltage-gated K+ channels

Electrophysiological investigations have previously suggested that phosphol ipase A(2) (PLA(2)) neurotoxins increase the release of acetylcholine (Ach) at the neuromuscular junction by blocking voltage-gated K+ channels in mot or nerve terminals. We have tested some of the most potent presynaptically-acting neurotoxins f rom snake venoms, namely beta -bungarotoxin (BuTx), taipoxin, notexin, crot oxin, ammodytoxin C and A (Amotx C & A), for effects on several types of cl oned voltage-gated K+ channels (mKv1.1, rKv1.2, mKv1.3, hKv1.5 and mKv3.1) stably expressed in mammalian cell lines. By use of the whole-cell configur ation of the patch clamp recording technique and concentrations of toxins g reater than those required to affect acetylcholine release, these neurotoxi ns have been shown not to block any of these voltage-gated K+ channels. In addition, internal perfusion of the neurotoxins (100 mug/ml) into mouse B82 fibroblast cells that expressed rKv1.2 channels also did not substantially depress K+ currents. The results of this study suggest that the mechanism by which these neurotoxins increase the release of acetylcholine at the neu romuscular junction is not related to the direct blockage of voltage-activa ted Kv1.1, Kv1.2, Kv1.3, Kv1.5 and Kv3.1 K+ channels. (C) 2001 Elsevier Sci ence Ltd. All rights reserved.