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 phospholipase A(2) (PLA(2)) neurotoxins from snake venoms increase the release of acetylcholine (Ach) at the neuromuscular junction by blocking voltage-gated K(+) channels in motor nerve terminals. We have tested some of the most potent presynaptically-acting neurotoxins from snake venoms, namely beta-bungarotoxin (BuTx), taipoxin, notexin, crotoxin, ammodytoxin C and A (Amotx C & A), for effects on several types of cloned 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 configuration of the patch clamp recording technique and concentrations of toxins greater than those required to affect acetylcholine release, these neurotoxins have been shown not to block any of these voltage-gated K(+) channels. In addition, internal perfusion of the neurotoxins (100 microg/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 neuromuscular junction is not related to the direct blockage of voltage-activated Kv1.1, Kv1.2, Kv1.3, Kv1.5 and Kv3.1 K(+) channels.
Fathi H
B
B
Department of Physiology and Pharmacology, University of Strathclyde, 27 Taylor Street, Glasgow G4 0NR, UK.
Rowan
E G
EG
Harvey
A L
AL
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D002038:Bungarotoxins / Q000494:pharmacology; D002478:Cells, Cultured; D002645:Chickens; D003001:Cloning, Molecular; D003439:Crotoxin / Q000494:pharmacology; D004546:Elapid Venoms / Q000201:enzymology* / Q000494:pharmacology*; D004594:Electrophysiology; D005347:Fibroblasts / Q000187:drug effects; D054501:Group II Phospholipases A2; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D009466:Neuromuscular Blocking Agents / Q000494:pharmacology*; D009469:Neuromuscular Junction / Q000187:drug effects* / Q000378:metabolism; D009498:Neurotoxins / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D010741:Phospholipases A / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects*; D014757:Viper Venoms / Q000494:pharmacology
D002038:Bungarotoxins; D004546:Elapid Venoms; D009466:Neuromuscular Blocking Agents; D009498:Neurotoxins; D015221:Potassium Channels; D014757:Viper Venoms; C005082:notexin; C015523:taipoxin; C020273:dendrotoxin; D003439:Crotoxin; C068117:ammodytoxin A; D010741:Phospholipases A; D054501:Group II Phospholipases A2; C060161:ammodytoxin C; D000109:Acetylcholine