Researchers at East Carolina University have found a muscle that doesn’t depend on oxygen like other muscles in the body. The finding has upended our understanding of how muscles work and may influence the future of medicine.
The muscle in question is the flexor digitorum brevis, or FDB. It’s the muscle at the bottom of the foot that curls the toes. Previously, we understood that all muscles require oxygen to create the energy needed to operate, but the FDB is different, says Espen Spangenburg, the director of the lab that published the study.
“We know it's still surviving after half a day. It's not necessarily working perfectly anymore, but 12 hours without oxygen, it's a long time to go,” Spangenburg said.
In comparison, most muscles last less than an hour without oxygen before losing functionality and deteriorating. Now, Spangenburg and his team didn’t set out to expose the FDB for its odd behavior, in fact, they stumbled upon it.
“I’m not going to pretend like we did it on purpose,” he said.
His colleague, Joe McClung was running experiments nearby to test treatments for peripheral arterial disease, a condition commonly associated with diabetes and high blood pressure, in which blood flow is restricted to the legs and feet. That trial involved depriving different foot muscles in mice of oxygen, but the FDB simply wouldn’t quit working.
“At first we thought we were doing something wrong experimentally," Spangenburg said. "We were making an error after a lot of checking our work, making sure that we weren't making a mistake, we finally came to the conclusion of hey, wait a minute. This is this isn't supposed to happen, but this is really unique and perhaps there's a way for us to leverage what's going on here.”
The discovery has made waves in the field of muscular biology, not only because it upends our understanding of how muscles work, but also because the FDB is commonly used in studies.
“I think we all as a field have to sit back and think about 'Wait, what does this mean?' he said, adding he's fielded questions from other researchers who use the muscle in experiments. "It's definitely caused some investigators to be concerned.”
It’s unclear just how the FDB continues to function under such extreme conditions – that's what Spangenburg’s lab is still trying to figure out.
Andrew Readyoff is a researcher in Spangenburg’s lab, helping to solve that question. He described a current experiment that involves extracting the FDB from mice.
“It’s a race against the clock, you have about 20-30 minutes before the muscle dies,” Readyoff said.
He then hooks the muscle up to a device that shocks the muscle, forcing it to contract, and measures the strength of that contraction. The experiment has generated heaps of data to help reveal the muscle doesn’t start off this way, but rather that it changes over time.
“We believe that the trait is an adapted trait, not an inherited," Spangenburg said. "It's not something that that the individuals born with. . . Now, we can't definitively prove why it's an adapted phenotype.”
Spangenburg’s lab compares the FDB muscle in mice at 4 weeks – just as they’re becoming independent – to the muscle at 8 and 12 weeks. He says the change occurs sometime within this timeframe. While they’re not sure what prompts the change, they do have some ideas.
“We think what's happening is the muscle is going through periods of intermittent loss of blood flow as the animal steps down on that foot and puts weight on it, it compresses the muscle," he said."We suspect that . . . that's what allows this phenotype to evolve.”
His lab doesn’t actively work with human patients, but they have seen a vibrant FDB compared to other muscles in people that suffer from peripheral arterial disease. While just an idea at this point, understanding how this muscle changes could help develop therapies for other parts of the body.
“The idea is we want to be able to hijack the biology behind it and then put it in the other cells that are really sensitive to loss of oxygen, like your heart, your brain," he said. "If we can find the biology that's allowing the FDB to do this, then we may be able to hijack some aspect of that biology to deliver a therapeutic that would allow a tissue to function even for a short amount of time or save it.”
Now that’s just a bit of optimistic speculation, but it’s not farfetched to believe that if one muscle can do it, then others can too. But that’s years in the future, Spangenburg says.
