Antifibrillatory Agents and Potassium Channels in the Atria: Pore Block versus Channel Trafficking

Two distinct mechanisms for acute inhibition of ion current. The classic approach to pharmacological manipulation of channel current is to block or inhibit the conduction of ions through the channel pore (right). As discussed in the text, a second approach is becoming increasingly clear by manipulating the trafficking of channel constituents in order to alter cell surface protein levels (left). One potential therapeutic mechanism would be the antiarrhythmic drug–induced internalization of Kv1.5 to early endosomal compartments. Certain drugs may operate through a combination of pore block and triggered internalization/redistribution of channel proteins.