Grant: CIHR New Investigator

This project is aimed towards better description of the molecular mechanism, which governs an inhibition of ion currents in cardiac K-channels by the novel anti-arrhythmic and anti-convulsant drugs. Selective transport of potassium ions across cellular membranes is a key component for the normal heart function. Theoretical simulations create a in silica model systems that allows in silica mutagenesis. Insights from models will then be validated or refuted by in vitro expression of native and mutated potassium channels followed by voltage clamp experiments. The information allows feedback refinement of the 3d molecular structure of the channels. The projects will lead to understanding of mechanisms of how membrane proteins select ions for their functional activity, of the mechanism of drug binding and block in different K+ channels, and structural determinants of cardiovascular diseases. Since inadvertent drug block is a major causes of Long QT Syndrome and potentially lethal arrhythmias in humans this work is clinically relevant.