Bothropstoxin-I reduces evoked acetylcholine release from rat motor nerve terminals: radiochemical and real-time video-microscopy studies.

摘要: Abstract Understanding the biological activity profile of snake venom components is fundamental for improving treatment snakebite envenomings and may also contribute development new potential therapeutic agents. In this work, we tested effects BthTX-I, a Lys49 PLA2 homologue from Bothrops jararacussu venom. While toxin induces conspicuous myonecrosis by catalytically independent mechanism, series in vitro studies support hypothesis that BthTX-I might exert neuromuscular blocking due to its ability alter integrity muscle cell membranes. To gain insight into mechanisms inhibitory effect, first time, influence on nerve-evoked ACh release was directly quantified radiochemical real-time video-microscopy methods. Our results show blockade produced exposure (1 μM) summation both pre- postsynaptic effects. Modifications affecting presynaptic apparatus were revealed significant reduction [3H]-ACh release; measurements transmitter exocytosis using FM4-64 fluorescent dye fully supported data. The effect characterized typical histological alterations in architecture skeletal fibers, increase outflow intracellular lactate dehydrogenase enzyme progressive depolarization resting membrane potential. conclusion, these findings suggest transient consequent general membrane-destabilizing subsequent decrease evoked motor nerve terminals.