Leftward Shift in the Voltage-Dependence for Ca super(2+) Currents Activation Induced by a New Toxin from Phoneutria reidyi (Aranae, Ctenidae) Venom

Various neurotoxins have been described from the venom of the Brazilian spider Phoneutria nigriventer, but little is known about the venoms of the other species of this genus. In the present work, we describe the purification and some structural and pharmacological features of a new toxin (PRTx3-7)...

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Bibliographic Details
Published in:Cellular and molecular neurobiology 2007-01, Vol.27 (1), p.129-146
Main Authors: Vieira, L B, Pimenta, AMC, Richardson, M, Bemquerer, M P, Reis, HJ, Cruz, J S, Gomez, M V, Santoro, M M, Ferreira-de-Oliveira, R, Figueiredo, S G, Snutch, T P, Cordeiro, M N
Format: Article
Language:English
Subjects:
Araneae
Ctenidae
Phoneutria
Phoneutria nigriventer
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Summary:Various neurotoxins have been described from the venom of the Brazilian spider Phoneutria nigriventer, but little is known about the venoms of the other species of this genus. In the present work, we describe the purification and some structural and pharmacological features of a new toxin (PRTx3-7) from Phoneutria reidyi that causes flaccid paralysis in mice. The observed molecular mass (4627.26 Da) was in accordance with the calculated mass for the amidated form of the amino acid sequence (4627.08 Da). The presence of an alpha -amidated C-terminus was confirmed by MS/MS analysis of the C-terminal peptide, isolated after enzymatic digestion of the native protein with Glu-C endoproteinase. The purified protein was injected (intracerebro-ventricular) into mice at dose levels of 5 mu g/mouse causing immediate agitation and clockwise gyration, followed by the gradual development of general flaccid paralysis. PRTx3-7 at 1 mu M inhibited by 20% the KCl-induced increase on [Ca super(2+)] sub(i) in rat brain synaptosomes. The HEK cells permanently expressing L, N, P/Q and R HVA Ca super(2+) channels were also used to better characterize the pharmacological features of PRTx3-7. To our surprise, PRTx3-7 shifted the voltage-dependence for activation towards hyperpolarized membrane potentials for L (-4 mV), P/Q (-8 mV) and R (-5 mV) type Ca super(2+) currents. In addition, the new toxin also affected the steady state of inactivation of L-, N- and P/Q-type Ca super(2+) currents.
ISSN:0272-4340
DOI:10.1007/s10571-006-9123-z