Heart: 60 year old mystery behind the lub-dub rhythm cracked, thanks to an IITian

New Delhi: A 60-year-old mystery on the functioning of the heart has finally been cracked, thanks to a young Indian researcher who provided vital clues on the genesis of the lub-dub rhythm of the most vital organ in the body.

Armed with a cryo-electron microscope and artificial intelligence tools, Debabrata Dutta at the University of Massachusetts Medical School uncovered the molecular structure of one of the two critical filaments in the heart muscles, responsible for pumping of the blood.

The lub-dub of the heart beat comes from the continuous contraction and expansion of heart muscles or more specifically from interactions between two protein filaments known as myosin and actin.

The two filaments slide over each other to make the heart muscles contract. After each beat, the heart enters a relaxed state, leading to filling of the chambers with blood before the next contraction, a process that continues, without a break, for the entire lifespan.

While the molecular structure of actin was found a few years ago, Dutta and his colleagues have now discovered the same for myosin, opening up a new window to look at heart complications. “This can lead to new drug discovery,” Dutta, who did his PhD from the Indian Institute of Technology, Kharagpur, told DH.

As the central players that make the heart a pump, actin and myosin proteins assemble into thin and thick filaments, respectively. Thin filaments have a fairly simple structure that is well understood. Thick filaments, on the other hand, are much more complex, and their structure has been difficult to determine.

Dutta’s team in the laboratory of Roger Craig at the Department of Radiology purified such thick filaments from human hearts, examining the specimens under conditions that correspond to the relaxation phase of the cardiac cycle, and determined the structure. “Preparing the sample itself was a big challenge,” he said.

The discovery becomes a major step forward from the basic structure of thick filaments outlined 60 years ago.

Dutta’s team, however, was not the only one to achieve this feat. Another group from the Max Planck Institute of Molecular Physiology at Dortmund, Germany also cracked the molecular structure of myosin using a slightly different approach. Both papers were published in Nature earlier this month.

“The vertebrate thick-filament structure that has been revealed by these studies is complex and almost bewildering. These papers mark the start of an exciting era,” said Peter J Knight, a senior scientist at the University of Leeds, UK, who is not associated with the research.

“At last, a structural framework is available on which to design new experiments, both to understand how muscle works and to try to find treatments for disease,” he wrote in an article in the same issue of Nature.