Molecular Basis of Voltage dependent-activation of HERG K+ channels

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The rhythm of the normal heart beat is controlled by electrical signals mediated by the flow of electrically charged atoms called ions. The flow of ions across heart cell membranes is predominantly mediated by proteins called ion channels that open and close in response to changes in the voltage across the cell membrane. One of these channels, called the HERG channel, has some unusual properties. Most notably, HERG channels open very slowly following an electrical stimulus, so slowly that they do not fully open until the end of the cardiac contraction cycle. These channels are therefore particularly well placed to help suppress arrhythmias initiated by premature or ectopic beats. We propose to undertake a detailed investigation into the mechanisms by which HERG channels open and close and to determine why activation of these channels is so slow. These results will provide a greater understanding of how HERG channels work and how the normal activity of HERG channels helps to suppress abnormal heart rhythms.