The Journal of Neuroscience, October 15, 1999, 19(20):8730-8739
A Scorpion 
-Like Toxin That Is Active on Insects and Mammals
Reveals an Unexpected Specificity and Distribution of Sodium Channel
Subtypes in Rat Brain Neurons
Nicolas
Gilles1,
Christophe
Blanchet2,
Iris
Shichor3,
Marc
Zaninetti2,
Ilana
Lotan3,
Daniel
Bertrand2, and
Dalia
Gordon1
1 CEA, Commissariat à l'Energie Atomique,
Département d'Ingénierie et d'Etudes des Protéines,
Saclay 91191, France, 2 Department of Physiology, C. M. U., CH 1211 Geneva 4, Switzerland, and
3 Tel-Aviv University, Sackler School of Medicine,
Department of Physiology and Pharmacology, Ramat Aviv, 69978 Israel
Several scorpion toxins have been shown to exert their neurotoxic
effects by a direct interaction with voltage-dependent sodium channels.
Both classical scorpion 
-toxins such as Lqh II from Leiurus
quiquestratus hebraeus and -like toxins as toxin III from
the same scorpion (Lqh III) competitively interact for binding on
receptor site 3 of insect sodium channels. Conversely, Lqh III, which
is highly toxic in mammalian brain, reveals no specific binding to
sodium channels of rat brain synaptosomes and displaces the binding of
Lqh II only at high concentration. The contrast between the
low-affinity interaction and the high toxicity of Lqh III indicates
that Lqh III binding sites distinct from those present in synaptosomes
must exist in the brain. In agreement, electrophysiological experiments
performed on acute rat hippocampal slices revealed that Lqh III
strongly affects the inactivation of voltage-gated sodium channels
recorded either in current or voltage clamp, whereas Lqh II had weak,
or no, effects. In contrast, Lqh III had no effect on cultured
embryonic chick central neurons and on sodium channels from rat brain
IIA and 
1 subunits reconstituted in Xenopus oocytes,
whereas sea anemone toxin ATXII and Lqh II were very active. These data
indicate that the -like toxin Lqh III displays a surprising subtype
specificity, reveals the presence of a new, distinct sodium channel
insensitive to Lqh II, and highlights the differences in distribution
of channel expression in the CNS. This toxin may constitute a
valuable tool for the investigation of mammalian brain function.
Key words:
scorpion -toxin; scorpion -like toxin; sodium
channel subtypes; receptor site 3; hippocampus slices; expression in
oocytes; chick central neurons; insect sodium channels; rat brain
synaptosomes
Copyright © 1999 Society for Neuroscience 0270-6474/99/19208730-10$05.00/0
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