Different effects of myotoxins bothropstoxin-I and II from Bothrops snake venom on cation transport ATPases from murine fast twitch skeletal muscle

Bothrops jararacussu venom drastically decreases sarcoplasmic Ca2+-ATPase (SERCA) protein expression in vivo and inhibits its activity in vitro, in contrast to a slight increase of Na+/K+-ATPase expression in murine EDL. We investigated the effect of myotoxins bothropstoxin-I and/or -II (BthTX-I, BthTX-II and BthTX-I+II) on this model. No changes were seen in SERCA1, SERCA2 and Na+/K+-ATPase α1 protein expression as well as 2+Ca-ATPase activity, but BthTX-II (1 μg/g) reduced Na+/K+-ATPase α2 expression by 50% one day after perimuscular injection. Interestingly, BthTX-II inhibited Ca2+-ATPase activity (IC50 around 6 nM). Our findings suggest that only BthTX-II affects ion transport ATPases, being a potent SERCA inhibitor and a putative target for antivenom drug development.