Novel spider toxin slows down the activation kinetics of P-type Ca2+ channels in Purkinje neurons of rat

• Published in: Toxicology (Amsterdam) 2005-02, Vol.207 (1), p.129-136
• Main Authors: Fisyunov, Alexander, Pluzhnikov, Kirill, Molyavka, Anton, Grishin, Eugene, Lozovaya, Natalia, Krishtal, Oleg
• Format: Article
• Language: English
• Subjects: Animals; Calcium Channels, P-Type - metabolism; Kinetics; Membrane Potentials - drug effects; Patch-Clamp Techniques; Peptides - pharmacology; Purkinje Cells - drug effects; Purkinje Cells - metabolism; Purkinje Cells - physiology; Rats; Rats, Wistar; Spider Venoms - chemistry; Toxins, Biological - pharmacology
• ISSN: 0300-483X
• DOI: 10.1016/j.tox.2004.09.005

We have identified a novel polypeptide toxin (Lsp-1) from the venom of the spider Lycosa (LS). Its effect has been examined on the P-type calcium channels in Purkinje neurons, using whole-cell patch-clamp. This toxin (at saturating concentration 7 nM) produces prominent (four-fold) deceleration of the activation kinetics and partial (71+/-6%) decrease of the amplitude of P-current without affecting either deactivation or inactivation kinetics. These effects are not use-dependent. They are partially reversible within a minute upon the wash-out of the toxin. Intracellular perfusion of Purkinje neurons with 100 microM of GDP or 2 microM of GTPgammaS, as well as strong depolarising pre-pulses (+100 mV), do not eliminate the action of Lsp-1 on P-channels indicating that down-modulation via guanine nucleotide-binding proteins (G-proteins) is not involved in the observed phenomenon. In view of extremely high functional significance of P-channels, the toxin can be suggested as a useful pharmacological tool.