Leftward Shift in the Voltage-Dependence for Ca2+ Currents Activation Induced by a New Toxin from Phoneutria reidyi (Aranae, Ctenidae) Venom |
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Authors: | L B Vieira A M C Pimenta M Richardson M P Bemquerer H J Reis J S Cruz M V Gomez M M Santoro R Ferreira-de-Oliveira S G Figueiredo T P Snutch M N Cordeiro |
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Institution: | Laboratório de Neurofarmacologia, Departamento de Farmacologia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil. |
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Abstract: | 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 α-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 μg/mouse causing immediate agitation
and clockwise gyration, followed by the gradual development of general flaccid paralysis. PRTx3-7 at 1 μM inhibited by 20%
the KCl-induced increase on Ca2+]i in rat brain synaptosomes. The HEK cells permanently expressing L, N, P/Q and R HVA Ca2+ 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 Ca2+ currents. In addition, the new toxin also affected the steady state of inactivation of L-, N- and P/Q-type Ca2+ currents.
L. B. Vieira and A. M. C. Pimenta contributed equally to this work. |
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Keywords: | Phoneutria reidyi spider venom neurotoxin amidated C-terminus Ca2+-channel toxin |
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