Ion Interactions in Cloned Potassium Channels

University Of Rochester, Rochester NY

Investigators

Abstract

The electrical activity of many organs is shaped by potassium selective ion channel proteins. Defects in potassium channels produce several types of electrophysiological disturbances including cardiac arrhythmias and epilepsy. These channels are the targets of many therapeutic drugs including the Class III anti-arrhythmic compounds. While many types of potassium channels have been cloned, many of their most basic properties, including ion discrimination and permeation, remain poorly understood. This project is designed to probe the mechanism of the interaction between tetraethylammonium ions (related to some Class III drugs) in the pore in these channels. This will be accomplished through a combination of molecular biological techniques with electrophysiological recordings and measurements of radio-labeled unidirectional ion fluxes. An additional component of this work will be the development of new forms of ion permeation models. These models will be developed as quantitative descriptions of the ion permeation mechanism but, more importantly, will be used to design new experiments and test competing mechanisms. A Web site will be established in order to facilitate wide distribution of these models for teaching and scientific uses. The results from this work will aid the understanding of selectivity and permeation in ion channel proteins. Since many therapeutic drugs interact with the pore in these channels and with ions in the pore, understanding the mechanisms of permeation and block may lead to the development of better drug therapies. The modeling tools that will be developed and broadly disseminated will help educate students and other scientists about these fundamental properties of ion channel proteins.