Abstract

α-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 α-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. © 2008 Elsevier Inc. All rights reserved.