Heart’s inner mechanisms to be studied with NIH grant

Jianmin Cui has received a nearly $1.7 million grant from the National Institutes of Health to study the molecular bases for the function of potassium channels vital for the heart, brain, inner ear and other tissues

Beth Miller 
Jianmin Cui

The five-year grant from the National Institute of Neurological Disorders and Stroke will allow Cui, professor of biomedical engineering in the School of Engineering & Applied Science at Washington University in St. Louis, to take a close look at some of the mutations in the potassium ion channels KCNQ1 and KCNE1 and their roles in cardiac disorders, including Long QT syndrome and cardiac arrhythmia.

In the heart, KCNQ1 works with KCNE1, an accessory subunit. When the two are put together, the combination changes the properties of the KCNQ1 channel so dramatically that scientists were once misled to believe that KCNE1 formed an entirely new channel on its own, rather than modifying an existing one. KCNQ1 is so important to the heart's rhythm that there are more than 250 mutations of the channel that have been associated with cardiac arrhythmia.

Specifically, Cui will analyze the mechanisms underlying the properties of these potassium ion channels, which will provide more insight into the diseases associated with the mutations. By better understanding these fundamentals, researchers will be able to develop better treatments that target the channels in the heart without affecting the same channels in the gut, thyroid or brain.

Cui proposes that a novel mechanism for activating KCNQ1 is behind these disorders, which can be fatal. Patients with Long QT syndrome who have mutations in KCNQ1 often experience symptoms of cardiac arrhythmia, such as fainting or sudden death, during exercise. Therefore, this study is significant to better understand long QT syndrome, Cui said.

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