The Underlying Workings of Muscle Function may Reveal How to Treat Heart Failure

Could the underlying workings of muscle function help researchers better understand how to treat heart failure?

New research will be taken on  by muscle physiologist Edward Debold at the University of Massachusetts Amherst's School of Public Health and Health Sciences, who's worked to advance the basic understanding of muscle functioning and increase future treatment options for 5.7 million Americans currently dealing with chronic heart failure.

"So for affected individuals the simplest tasks around the house become extremely arduous," Debold explained, via a news release. It makes sense to study the basis of skeletal muscle function, he added, "because if we can reduce the fatigue, we could enable them to live independently longer and increase activity levels, which can improve their long-term prognosis."

For quite some time, medical researchers and physiologists had believed that heart failure was simply a problem with the cardiac muscle, alone. Yet since the late 1980s, researchers have found that compromised function of the skeletal muscles also plays a part in the health issue, as well as much of the extreme fatigue experienced by many of the patients dealing with this problem.

"Our understanding of muscle fatigue is currently limited by our inability to directly observe this process at the molecular level," Debold added. "The really exciting aspect of this project is that it will overcome this limitation by using the latest technologies to directly visualize and characterize the process of muscle fatigue at the single-molecule level."

Debold and colleagues recently received a three-year, $198,000 grant from the American Heart Association to support further studies that could uncover the molecular mechanisms of skeletal muscle fatigue.

To conduct these experiments, lab researchers will initially isolate a 20-nanometer size muscle protein from skeletal muscle tissue and work to mimic the conditions of fatigue in a test tube. Next, they'll observe this impact on myosin's ability to generate both force and motion.

Researchers will specifically look to understand why metabolites slow and result in this fatigued state. Furthermore, they will also examine why a separate set of muscle proteins become less sensitive to molecular trigger calcium, including tropomyosin and troponin.

In the later stages of the project, researchers will work with pharmaceutical companies to start translating new knowledge on the condition by testing several drugs that specifically target contractile proteins myosin and troponin that help with fatigue.