Diversity of Potassium Channel Ligands: Focus on Scorpion Toxins

Potassium (K + ) channels are a widespread superfamily of integral membrane proteins that mediate selective transport of K + ions through the cell membrane. They have been found in all living organisms from bacteria to higher multicellular animals, including humans. Not surprisingly, K + channels bind ligands of different nature, such as metal ions, low molecular mass compounds, venom-derived peptides, and antibodies. Functionally these substances can be K + channel pore blockers or modulators. Representatives of the first group occlude the channel pore, like a cork in a bottle, while the second group of ligands alters the operation of channels without physically blocking the ion current. A rich source of K + channel ligands is venom of different animals: snakes, sea anemones, cone snails, bees, spiders, and scorpions. More than a half of the known K + channel ligands of polypeptide nature are scorpion toxins (KTx), all of which are pore blockers. These compounds have become an indispensable molecular tool for the study of K + channel structure and function. A recent special interest is the possibility of toxin application as drugs to treat diseases involving K + channels or related to their dysfunction (channelopathies).