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 Multi-year study finds 'hotspots' of ammonia over world's major agricultural areas
17.03.2017 | University of Maryland

nachricht Diabetes Drug May Improve Bone Fat-induced Defects of Fracture Healing
17.03.2017 | Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke

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: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

Im Focus: Researchers Imitate Molecular Crowding in Cells

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Argon is not the 'dope' for metallic hydrogen

24.03.2017 | Materials Sciences

Astronomers find unexpected, dust-obscured star formation in distant galaxy

24.03.2017 | Physics and Astronomy

Gravitational wave kicks monster black hole out of galactic core

24.03.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>