Discover the mysteries of muscle fatigue

Gina Kolata

One of the big questions that no answer in the field of physiology is: Why are you tired? This phenomenon is common in all organism, but the answer is still not possible until now.

Scientists in Colombia say they not only get the answer, but they can also build an experimental drug for mice that makes the animal regain consciousness, even though it can continue to run in one. Long time after collapsing due to exhaustion.

For decades, people have misunderstood and neglected muscle fatigue. According to Dr. Andrew Marks, principal project researcher, top physiological books cannot provide a mechanism to explain phenomena.There is a widely accepted theory that muscle fatigue is due to the release of suspected lactic acid recently .

A new explanation for muscle fatigue (Photo: Cameron Spencer / Getty Images)

In a report published online Monday in the Proceedings of the National Academy of Sciences , Dr. Marks said that the key lies in the flow of calcium inside muscle cells . Usually, the calcium in the cell controls muscle contraction, but when muscles become tired, the small tubes in the muscle lose calcium, causing muscle contraction to weaken. At the same time, the amount of calcium released stimulates an enzyme that erodes muscle fibers, contributing to muscle fatigue.

According to George Brooks (University of California, Berkeley), in recent years muscle researchers have more or less had discussions around why the problem is tired. George Brooks' own research questioned the lactic acid hypothesis.

What makes muscles tired?

According to Dr. Brooks, new experiments on mice are interesting and curious. The discovery came very casually from another field study. Dr. Marks, a cardiologist, wants to find better treatments for patients with congestive heart failure (a chronic form of depression that affects 4.8 million Americans). .

The hallmark of the disease is a damaged heart , usually from a heart attack or high blood pressure. When the heart pumps blood, it inflates; sometimes it becomes so big that it fills the patient's chest cavity. The more severe disease causes the lungs to overflow. Finally, the lungs are congested, the heart is almost unable to pump blood, the patient has difficulty breathing so he cannot walk in the room. Half of the patients died within 5 years.

To find out why the heart muscle is weakened, Dr. Marks focuses on molecular phenomena in the heart. He knew the sequence of phenomena. When a damaged heart tries to meet the body's need for blood supply, the nervous system stuffs the heart of the epinephrine and norepinephrine hormones, making the heart muscle cells contract more strongly.

Dr. Marks and colleagues discovered that contraction is enhanced because these two hormones bring calcium into the heart muscle cell's tubes.

However, neither epinephrine nor norepinephrine can stimulate the heart to meet the needs of the body's blood supply. The brain responds by releasing as many hormones until the hormones are produced continuously and relentlessly. At that time, the calcium tubes in the heart muscle cells were over-stimulated and began to lose calcium.

By understanding the mechanism, scientists studied a group of experimental drugs that inhibited the loss of calcium in the heart muscle . This group of drugs was originally created to inhibit calcium cells in cells, and this is also a way to lower blood pressure.

Dr. Marks and his colleagues changed the group of drugs to make them less toxic and eliminate their ability to inhibit calcium channels, leaving only the ability to prevent calcium leakage. Supervisors call the drug rycal because they bind to ryanodine receptors (calcium release tubes in heart muscle cells). They tested rycal drugs in mice and found they could prevent heart failure and arrhythmias in animals. Colombia has been granted a patent for this drug group. Armgo Pharma of New York is licensed for production. Dr. Marks is an advisor to the company.

Rycal drugs are expected to be tested safely on humans in the spring, but will not be conducted at Columbia due to dissent and supervisors. In the meantime, Dr. Marks wondered whether the mechanism he discovered could be applied to skeletal muscle as well as heart muscle. He said that skeletal muscle is similar to heart muscle and also has similar calcium tubing. And patients with asthenia complain that their muscular system is extremely weak.

Dr. Marks said: 'If you go to the hospital and ask a patient with heart failure what is bothering them. They will not say their hearts are weak. They say they are weak '.

Therefore, he and his colleagues observed that the lab rats had to work until they were exhausted, swimming and then running on a treadmill. Supervisors found calcium tubes in skeletal muscle began to leak. They gave the mice medicine. As a result, they can run longer distances from 10% to 20%.

In collaboration with Stephan Lehnart (a research scientist working at Appalachian State University - Boonetown, NC), supervisors have asked whether skeletal muscle in humans is suffering from a cause of loss. calcium?

Qualified cyclists participating in the experiment practiced on a stationary bike with high intensity for 3 hours a day, just like that for 3 consecutive days. For comparison, other cyclists must stand in the room but not practice.

Dr. Lehnart took the thighs of all the athletes after the third day and sent them to Colombia. There Dr. Marks' group will analyze muscle groups while not knowing which specimens belong to those who have been trained, which ones do not. According to Dr. Marks, the results are very clear. Calcium tubes in the muscles of the trainees leaked. A few days later, these muscle tubes healed themselves. Athletes return to normal.

Of course, although Dr. Marks wanted to create a drug for patients with congestive heart failure, it hoped to ease their fatigue and strengthen their heart function. But athletes may be tempted to take advantage of this drug when it is marketed.

However, opinions against the certification of this drug also made Dr. W. Robb McClellan (a heart disease researcher at UCLA) cautious."For heart failure, there are three drugs that can prolong life, but many people may have to test them up to 10 times," he said.

Dr. McClellan adds, even if the first drug that limits calcium loss does not work for patients, an important step has been achieved to understand the molecular phenomenon behind muscle fatigue. . He said: 'From there, we can study therapies'.

That day will come when there are anti-fatigue drugs

Dr. Steven Liggett, a heart failure researcher at the University of Maryland, thinks it's an 'amazing' idea . But he also said: 'For athletes, we need to wonder if it is necessary to break this mechanism. Maybe this is a protection mechanism. Maybe the fatigue phenomenon warns that you are entering a dangerous area. So it stops you. If you keep forcing yourself to run as fast as you can, some people will be able to keep running until they fall and die. '