Differential sensitivity of sodium channels from the central and peripheral nervous system to the scorpion toxins Lqh-2 and Lqh-3.
The scorpion alpha-toxins Lqh-2 and Lqh-3, isolated from the venom of the Israeli yellow scorpion Leiurus quinquestriatus hebraeus, were previously shown to be very potent in removing fast inactivation of rat skeletal muscle sodium channels (Chen et al., 2000). Here, we show that tetrodotoxin-sensitive neuronal channels NaV1.2 and NaV1.7, which are mainly expressed in mammalian central and peripheral nervous systems, respectively, are differentially sensitive to these two toxins. rNaV1.2 and hNaV1.7 channels were studied with patch-clamp methods upon expression in mammalian cells. While Lqh-3 was about 100-times more potent in removing inactivation in hNaV1.7 channels compared with rNaV1.2, Lqh-2 was about 20-times more active in the other direction. Site-directed mutagenesis showed that the differences in the putative binding sites for these toxins, the S3-4 linkers of domain 4, are of major importance for Lqh-3, but not for Lqh-2.
Chen
Haijun
H
Research Unit Molecular and Cellular Biophysics, Medical Faculty of the Friedrich Schiller University Jena, Drackendorfer St. 1, D-07747 Jena, Germany.
Lu
SongQing
S
Leipold
Enrico
E
Gordon
Dalia
D
Hansel
Alfred
A
Heinemann
Stefan H
SH
D000818:Animals; D002490:Central Nervous System / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D062551:NAV1.2 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000502:physiology; D017933:Peripheral Nervous System / Q000187:drug effects* / Q000502:physiology; D012604:Scorpion Venoms / Q000494:pharmacology*; D015222:Sodium Channels / Q000502:physiology*
C114938:Lqh II toxin; C114939:Lqh III toxin; D062551:NAV1.2 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C568251:SCN2A protein, human; C568253:Scn2A protein, rat; D012604:Scorpion Venoms; D015222:Sodium Channels