TsIV

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TsIV is a toxin from the venom of the Brazilian scorpion Tityus serrulatus. It is an alpha-scorpion toxin that binds to a specific spot (site 3 on domain IV) of sodium channels in cell membranes and slows their inactivation. This makes sodium channels stay open longer, increasing the electrical current and shifting activation and inactivation to more negative voltages. TsIV affects mammalian sodium channels in various cell types, not just one tissue.

In cells, TsIV slows the inactivation of sodium channels and raises peak current, without changing the time to peak. It’s not selective for a single tissue type and can affect sodium channels in rat heart cells, rat brain cells, and mouse skeletal muscle.

Clinical effects of Tityus serrulatus envenoming include local pain at the sting site and systemic symptoms such as vomiting, profuse sweating, agitation or restlessness, abnormal heart rhythms, blood pressure changes, possible heart failure or shock, rapid breathing or pulmonary edema, and lab abnormalities like high white blood cell counts, high blood sugar, and increased amylase.

Toxicity measurements in mice show TsIV is very potent: about 0.4 micrograms given under the skin or 24 nanograms injected into the brain ventricles for a 20 g mouse.

Treatment for Tityus bites uses intravenous antivenoms made in horses that have been immunized with a mix of venom from T. serrulatus and T. bahiensis.

Research has identified common epitopes shared by many Ts toxins, including TsIV, which could lead to antidotes that neutralize several different toxins. Studies have also examined how horse antisera react with synthetic pieces of Ts toxins to test their neutralizing potential.