TRANSFER OF THE SCORPION TOXIN RECEPTOR TO AN INSENSITIVE POTASSIUM CHANNEL

Voltage dependent potassium channels belong to a family of structurall y related cation channels that underlie the electrical activity of exc itable cells. Many potassium channels are blocked with high affinity b y scorpion toxins, whereas others are completely insensitive. We trans ferred toxin sensitivity from the highly sensitive Kv1.3 (KV3) to the insensitive Kv2.1 (DRK1) potassium channel by transferring the stretch of amino acids between transmembrane domains 5/6. We provide evidence that this S5-S6 linker, which has been shown to comprise the pore-for ming region, is probably the only part of the ion channel that directl y interacts with bound toxin. Using site-directed mutagenesis, we iden tified specific residues in the S5-S6 linker that are responsible for the acquisition of toxin sensitivity by Kv2.1.