Talare: Lipophilic potassium channel activators – possible anti-seizure and anti-arrhythmic treatments
Värd: Eric Chorell, Kemiska institutionen
Föreläsningen är på engelska
Voltage-gated ion channels play important roles in generating and shaping the electrical excitability of nerve and cardiac cells. While many drugs cause their effects by blocking the ion-conducting pore to prevent ion current, only a few exert their therapeutic effect by opening (or activating) the channel. Here I will present data from different types of lipophilic compounds that can activate voltage-gated potassium (Kv) channels. Negatively charged resin acids and polyunsaturated fatty acids affect the channel's positively charged voltage sensor, thereby opening the channel by pulling the sensor into an activated state. This interaction occurs at the interface between the phospholipid bilayer and the channel protein. In contrast, warfarin-like tautomers activate Kv1.5 channels by affecting the linker connecting the voltage sensor and the ion-conducting pore domain of the channel. Characterizing different binding sites and compounds that use them on different ion channels will hopefully lead to better treatments for diseases caused by altered excitability, for instance epilepsy.