A novel depolarizing activity of scorpion venom fraction M1 due to activation of skeletal muscle nicotinic receptors

Laboratoire des Venins et Toxines, Institut Pasteur de Tunis, Tunis BP 74-1002, Tunisia.
Toxicon (Impact Factor: 2.49). 02/2007; 49(1):117-22. DOI: 10.1016/j.toxicon.2006.09.011
Source: PubMed


A depolarizing activity following interaction with nicotinic acetylcholine receptors (nAchRs) in skeletal muscle cells, was observed for the first time in the non-toxic venom fraction (M1) of the yellow scorpion Buthus occitanus tunetanus (Bot). The effects of M1 fraction were tested on cultured rat myotubes by recording changes in [Ca2+]i. When applied, M1 (10 microg/mL) induced a transient increase of [Ca2+]i which could be blocked by a prior application of alpha-Bungarotoxin (alpha-Bg-Tx).

Download full-text


Available from: Rym Benkhalifa,
  • Source
    • "skeletal muscle cells (Cheikh et al., 2007), and inhibition of cardiac L-type calcium currents (Cheikh et al., 2006). Within the nine HPLC fractions of M2, only the subfraction called P8 displayed K v 7.4-activating properties. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Kv7.4 channel subunits are expressed in central auditory pathways and in inner ear sensory hair cells, skeletal and smooth muscle cells. Openers of Kv7.4 channels have been suggested to improve hearing loss, systemic or pulmonary arterial hypertension, urinary incontinence, gastrointestinal and neuropsychiatric diseases, and skeletal muscle disorders. Scorpion venoms are a large source of peptides active on K(+) channels; therefore, a combined purification/screening procedure has been optimized in the present work to identify specific modulator(s) of Kv7.4 channels from the venom of the North African scorpion Androctonus australis (Aa). We report the isolation and functional characterization of AaTXKβ(2-64), a novel variant of AaTXKβ(1-64) in an HPLC fraction from the Aa venom (named P8), which acted as the first peptide activator of Kv7.4 channels. In particular, in both Xenopus oocytes and mammalian CHO cells, AaTXKβ(2-64), but not AaTXKβ(1-64), hyperpolarized the threshold voltage of current activation and increased the maximal currents of heterologoulsy-expressed Kv7.4 channels. AaTXKβ(2-64) also activated Kv7.3, Kv7.2/3, and Kv7.5/3 channels, whereas homomeric Kv1.1, Kv7.1, and Kv7.2 channels were unaffected. We anticipate that these results might prove useful to unravel novel biological roles of AaTXKβ(2-64)-sensitive Kv7 channels, and to develop novel pharmacological tools allowing subtype-selective targeting of Kv7 channels.
    Molecular pharmacology 09/2013; 84(5). DOI:10.1124/mol.113.088971 · 4.13 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Scorpion envenoming is less studied in pregnant victims. In this work, the effect of Buthus occitanus tunetanus on parturition in late pregnancy was studied in an animal model. Four groups of six primigravid female rats, each one at the 22nd day of pregnancy, were used. The first two groups had received an intra-peritoneal injection of 500 microg/kg of Buthus occitanus tunetanus crude venom or a physiological saline solution and left until foetal delivery. Then, the time elapsed until the first pup delivery and that separating the first and latest ones were measured. The other two groups served for the uterine electrophysiological activity exploration. Rats were anaesthetized, artificially ventilated and had received an intraperitoneal injection of 500 microg/kg of Buthus occitanus tunetanus crude venom or a physiological saline solution. Our results showed a significant increase of the latency to foetal delivery, labour time, and uterine contractile activity in envenomed rats compared to controls. Such signs are usually seen in dynamic dystocia. It was concluded that Buthus occitanus tunetanus envenoming might induce a dynamic dystocia, when it occurred in late pregnancy.
    Comptes Rendus Biologies 01/2008; 330(12):890-6. DOI:10.1016/j.crvi.2007.09.001 · 0.98 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Scorpion envenomation is a public health problem in Venezuela, mainly produced by Tityus discrepans (TD) and Tityus zulianus (TZ). Accidents by these two species differ clinically. Thus, TZ envenomation is associated with high mortality in children due to cardiopulmonary disorders, as a result of, excessive amounts of plasma catecholamines (Epinephrine) release from adrenal medulla, probably via the voltage-gated sodium-channel activated by specific scorpion toxins. This Epi release is, in part responsible, for some of the envenomation clinical consequences, resembling those described for patients presenting catecholamine-releasing tumors (pheochromocytoma). In this work, BALB/c mice and rat pheochromocytoma-derived PC12 cells were used to provide in vivo and in vitro models, respectively, on which the basis for the TZ-mediated catecholamine release mechanism could be elucidated. In mice, TZ venom increased, at 1h post-injection, the Epi plasma levels in 4000%, which remained elevated for 24h. A significant rise in plasma levels of the catecholamine catabolite 3-Methoxy-4-Hydroxy-Phenyl-Glycol (MHPG) was also observed. In [(3)H]dopamine-loaded PC12 cells, TZ venom potentiated the carbamylcholine (CC)-mediated release of [(3)H]dopamine, as shown by the leftward shift in the CC-dose-response curves. Moreover, TZ venom also displayed the maximal [(3)H]dopamine releasing activity compared to TD venom, with significant reduction of the EC50 for CC. The nicotinic-acetylcholine receptor (nAChR) blocker hexamethonium induced a significant inhibition of the [(3)H]dopamine release produced by CC in PC12 cells but the TZ-elicited release of [(3)H]dopamine was 70% hexamethonium-insensitive, suggesting unidentified TZ toxins affecting other regulatory mechanisms of catecholamine secretion.
    Toxicon 11/2011; 59(1):117-23. DOI:10.1016/j.toxicon.2011.10.013 · 2.49 Impact Factor
Show more