Helping a defective ion channel protein get to its correct location in long QT syndrome

Rescuing defective trafficking of mutant channel complexes in the long QT syndrome

Long QT syndrome (LQTS) is a condition that can cause an irregular heartbeat (arrhythmia) due to abnormal electrical activity in the heart. An inherited form of LQTS, called long QT syndrome type 1 (LQT1), is a cause of sudden cardiac death in young people. Nearly half of people with LQT1 have a genetic mutation in a gene called KCNQ1. KCNQ1 forms part of a structure called an ion channel. Ion channels span the membrane of heart cells and allow charged atoms (ions) to flow in and out, creating an electrical current. Many of the KCNQ1 mutations that cause LQT1 are thought to prevent KCNQ1 from being transported to its correct location in the cell membrane. Thus, normal electrical activity does not occur, increasing the risk of arrhythmias. Dr Stephen Harmer and his team at the University of Bristol will lead a project to identify ways to help mutated forms of KCNQ1 reach their correct location in the membrane of heart cells. Specifically, the researchers will study heart cells to find out where the defective KCNQ1 ion channels end up. Precisely, they will look at why KCNQ1 ion channels are not transported to the right place. They will also screen a library of small molecules to see if any are able to restore the transportation of KCNQ1 to its correct location. This research could lead to new treatments to restore normal electrical activity in the hearts of people with inherited LQTS, thus drastically reducing the risk of fatal arrhythmias.