Potassium channel blockers from the venom of the Brazilian scorpion Tityus serrulatus ( Lutz and Mello, 1922)

• The venom from the Brazilian scorpion Tityus serrulatus contains small peptidic toxins able to block various K+ channels.
• Toxins from the external side structurally obstruct the K+ channel’s conducting pore.
• The structures and mechanisms of action of the toxin-blockers so far identified in the Tityus serrulatus venom are analyzed.
• Recent proteomic and transcriptomic data are correlated with previous biochemical results and discussed.

Potassium (K+) channels are trans-membrane proteins, which play a key role in cellular excitability and signal transduction pathways. Scorpion toxins blocking the ion-conducting pore from the external side have been invaluable probes to elucidate the structural, functional, and physio-pathological characteristics of these ion channels. This review will focus on the interaction between K+ channels and their peptide blockers isolated from the venom of the scorpion Tityus serrulatus, which is considered as the most dangerous scorpion in Brazil, in particular in Minas-Gerais State, where many casualties are described each year. The primary mechanisms of action of these K+ blockers will be discussed in correlation with their structure, very often non-canonical compared to those of other well known K+ channels blockers purified from other scorpion venoms. Also, special attention will be brought to the most recent data obtained by proteomic and transcriptomic analyses on Tityus serrulatus venoms and venom glands.