The Function of the KCNQ1 Potassium Ion Channel in the Human Heart

Abstract

KCNQ1 is a homotetrameric voltage‐gated potassium ion channel subunit protein. KCNQ1 is the alpha‐subunit of the ion channel and forms heteromultimers with protein members of the KCNE family (“beta subunits”) to create a pore in the membrane of a cell. Two of these beta subunits are KCNE1 and KCNE3. Under physiological conditions, four KCNQ1 alpha subunits combine with two or four beta subunits to form the potassium ion channel. The alpha subunits form the structure of the channel whereas the beta subunit binds onto the channel and regulates its activity. KCNQ1 is embedded in the membranes of numerous types of cells, including cardiac myocytes, epithelial cells, and cells in the human inner ear. In human cardiac myocytes, KCNQ1 and KCNE1 work to regulate the rhythm of the heart by controlling the repolarization phase of the cardiac action potential. Almost three hundred mutations have been identified in the KCNQ1 gene, which is located on chromosome 11. The majority of these are missense mutations and alter the protein's structure to the extent that the flow of potassium ions out of the cardiac cells is disrupted. The most common condition resulting from a mutation in KCNQ1 in hereditary Long QT Syndrome (LQTS), which is characterized by a delay in the ventricular repolarization component of a heart beat. Symptoms associated with LQTS include dizziness, fainting, and potentially seizures and sudden death. In rare cases, a mutation in KCNQ1 can also cause further complications, which include atrial fibrillation, Short QT syndrome, and Jervell and Romano‐Ward syndrome. Treatments are available for LQTS, such as making lifestyle changes, taking beta blockers, and implanting a defibrillator. Current research in medication for LQTS is centered around compounds such as hexachlorophene that can target the individual subunits in the ion channel as opposed to the entire channel. Pairing compounds with this ability may provide enough correction to the subunits that LQTS can be effectively “cured.” The Walton High School SMART Team has designed a 3D model of the KCNQ1 ion channel using JMOL to investigate the relationship between structure and function.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.