Proteins needed to produce stable heartbeat identified

Scientists have identified six proteins that coordinate heart cells to produce a stable heartbeat.

Researchers at Cedars-Sinai Heart Institute in US found that the smallest of these proteins directs the largest in performing its role of coordinating billions of heart cells during each heartbeat.

Together, the proteins synchronise the beating heart, the researchers determined.

"We now know these proteins exist," said Robin Shaw, the senior author of the study published in the journal Cell Reports.

"The findings advance our understanding of cell-to-cell communication at the root of healthy heart function. When there is less cell communication, which occurs in failing hearts, chances are greater of disturbances in heart rhythm that can result in disability or death," Shaw said.

Until now, scientists had recognised just one protein involved in cell-to-cell communication that occurs through conduits known as "gap junctions."

The Cedars-Sinai researchers identified five additional proteins that regulate the rapid flow of electrical communication signals, coordinating heart cells to produce a stable heartbeat.

"The finding of alternative translation start sites within this important group of proteins adds startling diversity to a key biological process, namely that whereby heart cells communicate with each other electrically," said Eduardo Marban, director of the Cedars-Sinai Heart Institute.

"The implications are major for arrhythmias and heart failure," Marban said.

Through a phenomenon called "alternative translation," the protein-making machinery in each cell can produce shorter proteins from the same gene that encodes the largest of the proteins.

Biologists had known of the existence of alternative translation but had not completely understood its physiological relevance.

The Cedars-Sinai research team has expanded the understanding of this process.

The researchers have also determined that a class of drugs known as "mTOR inhibitors" - those already used for immunosuppression in organ transplants - can affect alternative translation, changing the balance of proteins in hearts cells, increasing the amount of electrical coordination in the heart.

The findings suggest that mTOR inhibitors can be used to prevent erratic and sometimes fatal heart rhythms.