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

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Electrophysiological investigations have previously suggested that phospholipase A2 (PLA2) 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 β-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 μg/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.
LanguageEnglish
Pages1871-1882
Number of pages11
JournalToxicon
Volume39
Issue number12
DOIs
Publication statusPublished - Dec 2001

Fingerprint

Snake Venoms
Phospholipases
Neuromuscular Junction
Neurotoxins
Voltage-Gated Potassium Channels
Acetylcholine
Electric potential
Crotoxin
Cells
Bungarotoxins
Phospholipases A2
Clamping devices
Patch-Clamp Techniques
Fibroblasts
Perfusion
Cell Line

Keywords

  • beta-bungarotoxin
  • taipoxin
  • notexin
  • crotoxin
  • ammodytoxin
  • phospholipase A(2)
  • voltage-gated K+ channels
  • neuromuscular junction
  • acetylcholine release

Cite this

@article{7c581c13be00429993edfd8043e56980,
title = "The facilitatory actions of snake venom phospholipase a(2) neurotoxins at the neuromuscular junction are not mediated through voltage-gated k+ channels",
abstract = "Electrophysiological investigations have previously suggested that phospholipase A2 (PLA2) 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 β-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 μg/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.",
keywords = "beta-bungarotoxin, taipoxin, notexin, crotoxin, ammodytoxin, phospholipase A(2), voltage-gated K+ channels, neuromuscular junction, acetylcholine release",
author = "B. Fathi and E.G. Rowan and A.L. Harvey",
year = "2001",
month = "12",
doi = "10.1016/S0041-0101(01)00170-2",
language = "English",
volume = "39",
pages = "1871--1882",
journal = "Toxicon",
issn = "0041-0101",
number = "12",

}

TY - JOUR

T1 - The facilitatory actions of snake venom phospholipase a(2) neurotoxins at the neuromuscular junction are not mediated through voltage-gated k+ channels

AU - Fathi, B.

AU - Rowan, E.G.

AU - Harvey, A.L.

PY - 2001/12

Y1 - 2001/12

N2 - Electrophysiological investigations have previously suggested that phospholipase A2 (PLA2) 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 β-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 μg/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.

AB - Electrophysiological investigations have previously suggested that phospholipase A2 (PLA2) 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 β-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 μg/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.

KW - beta-bungarotoxin

KW - taipoxin

KW - notexin

KW - crotoxin

KW - ammodytoxin

KW - phospholipase A(2)

KW - voltage-gated K+ channels

KW - neuromuscular junction

KW - acetylcholine release

UR - http://dx.doi.org/10.1016/S0041-0101(01)00170-2

U2 - 10.1016/S0041-0101(01)00170-2

DO - 10.1016/S0041-0101(01)00170-2

M3 - Article

VL - 39

SP - 1871

EP - 1882

JO - Toxicon

T2 - Toxicon

JF - Toxicon

SN - 0041-0101

IS - 12

ER -