Brief communication Synaptic effects of low molecular weight components from Chilean Black Widow spider venom Jorge Parodi *, Fernando Romero Laboratorio de Neurociencia-CEBIOR, Departamento de Ciencia Preclinicas, Facultad de Medicina, Universidad de la Frontera, Montevideo 0870, Temuco, Chile 1. Introduction The Chilean spider Latrodectus mactans pertains to the genus Latrodectus which is found worldwide (Garb et al., 2004) and is known as the ‘‘Wheat Spider’’ or ‘‘Black Widow’’ and inhabits various regions of Chile. The bite from this spider in humans produces a systemic effect called latrodectism or systemic latrodectism and in some cases results in death (Schenone and Correa, 1985). Venom collected from Chilean L. mactans in the VIII and IX regions of Chile was shown to induce a sustained tonic effect in cardiac and smooth muscle (Romero et al., 2003). In smooth muscle, the mechanism of contraction is related to the permeability of Na + and Ca 2+ ions which modulate the contractile response (Nouailhetas et al., 1985) that has a fast, phasic component followed by a slower more sustained tonic component (Shimuta et al., 1982). Our studies in the deferent vessel of the rat revealed that the effect induced by the L. mactans venom is partially dependent of adrenergic and cholinergic mediators (patent pending). These results raise ques- tions about the mechanism of action of the toxin on smooth muscle. We postulated ionic mechanism, to explain same of these systemic effects, based in the idea of described effects of low-molecular component from Black Widow venom, over muscle and alteration the cellular physiology (Kiyatkin et al., 1992; Grishin et al., 1993). It has been postulated that potassium currents, for the importance of these currents in the regulation of muscle contraction and the participation over calcium homeostatic (Sanborn, 2000). A classic synaptic model was affects for a-latrotoxin and high-molecular weight peptides (Auger and Marty, 2000) and dependent of potassium channels for normal regulation of synaptic activity (Pan and Stringer, 1997). We tested the effect of Chilean venom in hippocampal neuron, and reported the changes in synaptic activity, for have synaptic effects under control and postulate, mechanism over neuromuscular union. For another way, we choice a basic model of cell lines, for observation of passive electric properties of membrane and not showed receptor or increased number of channels (Varghese et al., 2006). For these reason used HEK 293 cells for the observation of changes in membranes conductance. In the present study was to analyze the possible participation of potassium conductance on the systemic effects observed with the venom of L. mactans, recording cellular effects associated a changes in potassium conductance in neurons and cells lines. NeuroToxicology xxx (2008) xxx–xxx ARTICLE INFO Article history: Received 23 May 2008 Accepted 27 August 2008 Available online xxx Keywords: Synapses Venom Spider Toxic Black Widow ABSTRACT a-Latrotoxin is the principal component of the venom from the euroasiatic Black Widow spider and has been studied for its pharmacological use as a synaptic modulator. Interestingly, smaller molecular weight fractions have been found to be associated with this toxin, but their cellular actions have not been studied in detail. The venom from the Chilean Black Widow spider (Latrodectus mactans) does not produce a- latrotoxin, however it does contain several small polypeptides. We have recently demonstrated cellular effects of these peptides at the synaptic level using whole-cell patch clamp techniques. Purified venom from the glands of L. mactans was studied in 12 DIV rat hippocampal neuronal cultures. Venom at a concentration of 10 nM was able to decrease neuronal conductance thereby increasing membrane resistance. This effect on the passive properties of the neurons induced a change in action potential kinetics simulating the action of classic potassium channel blockers. These changes produced an increase in spontaneous synaptic activity in rat hippocampal cultures in the presence of the venom in a concentration- and time-dependent manner. These results indicate that venom from Chilean spider L. mactans is capable of increasing cell membrane resistance, prolonging the action potential and generating an increase in synaptic activity demonstrating an interesting pharmacological effect of these low molecular weight fragments. ß 2008 Elsevier Inc. All rights reserved. * Corresponding author at: Laboratorio de Neurociencia-CEBIOR, Facultad de Medicina, Universidad de la Frontera, Montevideo 0870, Temuco, Chile. Tel.: +56 45 734041. E-mail address: jparodi@ufro.cl (J. Parodi). G Model NEUTOX-899; No of Pages 6 Please cite this article in press as: Parodi J, Romero F. Synaptic effects of low molecular weight components from Chilean Black Widow spider venom, Neurotoxicology (2008), doi:10.1016/j.neuro.2008.08.006 Contents lists available at ScienceDirect NeuroToxicology 0161-813X/$ – see front matter ß 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.neuro.2008.08.006