Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers show leaky muscle cells lead to fatigue

12.02.2008
What slows down marathoners may also tire heart failure patients; experimental drug that improves endurance may provide patients with relief from exhaustion

What do marathoners and heart failure patients have in common? More than you think according to new findings by physiologists at Columbia University Medical Center.

The new study shows that the fatigue that marathoners and other extreme athletes feel at the end of a race is caused by a tiny leak inside their muscles that probably also saps the energy from patients with heart failure.

The leak – which allows calcium to continuously leak inside muscle cells – weakens the force produced by the muscle and also turns on a protein-digesting enzyme that damages the muscle fibers. The new study found the leak was present in the muscle of mice after an intense three-week daily swimming regimen and in human athletes after three days of daily intense cycling. The same leak was previously discovered by Marks and colleagues in the muscles of animals with heart failure.

The new study also found that an experimental drug developed by the researchers alleviated muscle fatigue in mice after exercise, suggesting that the drug also may provide relief from the severe exhaustion that prevents patients with chronic heart failure from getting out of bed or fixing dinner.

The results will be published in the online edition of the Proceedings of the National Academy of Sciences at 5 p.m. ET on February 11, 2008.

“The study does not mean exercise is bad for you,” says the study’s senior author, Andrew Marks, M.D., chair of the Department of Physiology and Cellular Biophysics, and director of the Clyde and Helen Wu Center for Molecular Cardiology at Columbia University Medical Center. “We only saw the leak in animals and human athletes that exercised three hours a day at very high intensities for several days or weeks in a row until they were exhausted.” He notes that athletes’ muscles also will return to normal after several days of rest and any muscle damage will be repaired after several days or weeks depending on the degree of exercise.

However, the arm, leg and breathing muscles of patients with heart failure never have a chance to recover. “People with chronic heart failure are subject to this same kind of muscle leak and damage constantly even without doing any exercise,” Marks says. “One of these patients’ most debilitating symptoms is muscle weakness and fatigue, which can be so bad they can’t get out of bed, brush their teeth, or feed themselves.”

This fatigue experienced by heart failure patients does not stem from a reduction in the amount of blood and oxygen supplied to the muscles by the heart, as one might expect. Instead, Marks’ previous research in muscles of mice with heart failure suggested that fatigue in patients stems from the calcium leak, which reduced the ability of a single muscle to contract repeatedly before losing force.

“We then had a hunch that the process that produces fatigue in heart failure patients also may be responsible for the fatigue felt by athletes after a marathon or extreme training,” says the study’s first author, Andrew Bellinger, Ph.D., who is currently finishing his M.D. at Columbia University’s College of Physicians & Surgeons. “Our new paper shows that fatigue in both patients and athletes probably stems from the same leak.”

Fatigue Can Be Alleviated With Experimental Drug

The researchers then used the similarity between athletes and patients to their advantage to see if an experimental drug could increase exercise capacity and reduce fatigue.

The researchers gave the drug – which plugs the leak of calcium – to mice before the animals started a 3-week regimen of swimming. Without the drugs, mice are exhausted after three weeks of daily 3-hour swims. With the drug, the mice were still energetic, had lost less exercise capacity after 3 weeks, and their muscles showed fewer signs of calcium leakage, atrophy, and less muscle damage.

The cyclists in the current study were not given the drug, which is not yet available for people.

Plans are underway to test the drug at other medical centers in patients with heart failure to see if it relieves fatigue and improves heart function. Even if successful, it will take several years before the drug will be commercially available.

Study Also Provides Explanation for Muscle Fatigue Besides Lactic Acid

The calcium leak also provides a new explanation for the muscle soreness and fatigue that marathoners and other athletes can experience for weeks after crossing the finish line.

Physiologists have recently largely discarded the 100 year-old theory that lactic acid accumulation in the muscle cells produces fatigue and limits athletic performance. New theories have been exploring the role of calcium in this process. The involvement of defects in calcium handling in limiting muscle performance and producing exercise fatigue makes sense because the flow of calcium in and out of the muscle cell controls muscle contraction.

The discovery of the calcium leak in fatigued animals and athletes is the first time anyone has pinpointed a precise mechanism for the involvement of a defect in calcium handling in limiting exercise capacity.

Elizabeth Streich | EurekAlert!
Further information:
http://www.columbia.edu
http://www.cumc.columbia.edu

More articles from Studies and Analyses:

nachricht Real-time feedback helps save energy and water
08.02.2017 | Otto-Friedrich-Universität Bamberg

nachricht The Great Unknown: Risk-Taking Behavior in Adolescents
19.01.2017 | Max-Planck-Institut für Bildungsforschung

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Microhotplates for a smart gas sensor

22.02.2017 | Power and Electrical Engineering

Scientists unlock ability to generate new sensory hair cells

22.02.2017 | Life Sciences

Prediction: More gas-giants will be found orbiting Sun-like stars

22.02.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>