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Studying muscle function to advance treatment of heart failure
Date:8/6/2014

ons of myosin, the protein that makes muscles contract.

Debold, who built the laser trap assay at UMass Amherst, says, "We're one of only a handful of in the world labs who have an instrument capable of making these measurements. The techniques are new, so no one has addressed the mechanisms of muscle fatigue in quite this way, using the laser trap assay. It should help us to figure out why a muscle stops working during fatigue."

To do these experiments the lab initially isolates the 20-nanometer size muscle protein myosin (one million times smaller than a millimeter) from skeletal muscle tissue. They will then mimic the conditions of fatigue in a test tube and directly observe the impact on myosin's ability to generate force and motion.

One of the basic ideas to be tested is how and why the presence of metabolites act to slow the velocity of contraction in fatigued muscles. A second aim is to understand how these same metabolites disrupt the regulation of muscle contraction, specifically why a separate set of muscle proteins, tropomyosin and troponin, become less sensitive to their molecular trigger calcium.

Debold explains, "We believe this process is disrupted during fatigue and muscles become less sensitive to calcium, the ion released in muscle cells in response to stimulation from a nerve. This means that even though your brain is telling the muscle to contract strongly, you get less force because the muscle doesn't respond as well to the signal from the brain."

In a later phase of the project, Debold and his colleagues will partner with pharmaceutical companies to begin to translate their new knowledge about muscle fatigue by testing several drugs that target the contractile proteins myosin and troponin to enhance their function under fatigue like conditions. This represents a crucial first step in the translation of this knowledge from the lab bench to the patient's bedside.

This is a highly collabor
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Contact: Janet Lathrop
jlathrop@admin.umass.edu
413-545-0444
University of Massachusetts at Amherst
Source:Eurekalert  

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