New Target Discovered for Treating Atrial Fibrillation
Introduction
Researchers at the University of Arizona College of Medicine-Phoenix and the University of California Davis Health have identified a new target for developing a treatment for atrial fibrillation (AFib), the most common type of irregular heart rhythm.
Atrial Fibrillation and Its Impact
Atrial fibrillation, also known as AFib or AF, is responsible for about one in seven strokes, according to the U.S. Centers for Disease Control and Prevention (CDC). This condition significantly increases the risk of health complications and death. The American Heart Association (AHA) estimates that more than 12 million people in the U.S. will suffer from AFib by 2030, and existing treatment methods are currently inadequate.
Research Focus: SK Channels
For a long time, scientists have studied heart-related proteins as possible treatment targets for AFib. A key focus has been on small-conductance calcium-activated potassium channels (SK channels). However, past research showed mixed results when attempting to inhibit these channels, with the possibility of either reducing or worsening arrhythmias depending on the conditions.
Breakthrough Study on SK2 Channels
In this new study, Dr. Nipavan Chiamvimonvat, Chair of Basic Medical Sciences at the University of Arizona College of Medicine-Phoenix, explained that the team used cutting-edge experimental and computational methods to study how the SK2 channel, a type of SK channel, is regulated. This research is timely because SK channel inhibitors are already being tested in clinical trials for AFib, so understanding how they work is crucial.
Role of PIP2 in Heart Function
The study, published in the journal Proceedings of the National Academy of Sciences, focused on a lipid called phosphatidylinositol 4,5-bisphosphate (PIP2), which helps regulate the SK2 channel. PIP2 is found in all cell membranes and plays an important role in various signaling pathways in the body.
According to Dr. Ryan Woltz, co-first author and computational biologist at the University of Arizona, regulating heart ion channels through PIP2 is a newly discovered mechanism that can influence how the heart functions.
Implications for Heart Failure
SK channels are the only known potassium channels that are upregulated (increased in activity) during heart failure, and this regulation is essential to understanding how disturbances in heart rhythms occur. The study showed that since PIP2 is often dysregulated during heart failure, it may be a key factor in cardiac arrhythmias.
Dr. Yang Zheng, another co-first author and postdoctoral research fellow, stated that the study’s findings offer important insights into how heart rhythm problems develop, especially in the context of heart failure.
Designing New Treatments for AFib
The research team used computational models to simulate how the SK2 channel behaves in different states (closed, intermediate, and open) and how PIP2 affects its activity. According to Dr. Vladimir Yarov-Yarovoy from UC Davis Health, the study’s structural findings will help in designing new SK2 channel inhibitors for treating heart rhythm disorders like AFib.
Future Research and Collaboration
Dr. Igor Vorobyov, the co-senior author from UC Davis Health, shared that the research team is already using these advanced techniques to study other SK channel subtypes. He expressed excitement about continuing this collaborative work, which could lead to drugs that either enhance or inhibit the function of these channels, offering new treatment options for AFib and other cardiovascular conditions.
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