Novel spider toxin slows down the activation kinetics of P-type Ca2+ channels in Purkinje neurons of rat.
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.
Fisyunov
Alexander
A
Department of Cellular Membranology, A.A. Bogomoletz Institute of Physiology, Bogomoletz Street 4, Kiev 01024, Ukraine.
Pluzhnikov
Kirill
K
Molyavka
Anton
A
Grishin
Eugene
E
Lozovaya
Natalia
N
Krishtal
Oleg
O
D000818:Animals; D020865:Calcium Channels, P-Type / Q000378:metabolism*; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000494:pharmacology*; D011689:Purkinje Cells / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013111:Spider Venoms / Q000737:chemistry*; D014118:Toxins, Biological / Q000494:pharmacology*
D020865:Calcium Channels, P-Type; D010455:Peptides; D013111:Spider Venoms; D014118:Toxins, Biological