Beta Protein of Sodium Pump Plays Role in Heart

A team of researchers led by Ayyappan K. Rajasekaran, PhD, Director of the Nemours Center for Childhood Cancer Research at the Alfred I. duPont Hospital for Children has shown that the beta-subunit of sodium pump plays a critical role in heart function. The findings were published in the Journal of Molecular and Cellular Cardiology (47 (2009), pp. 552-560).

Dr. Rajasekaran’s team had previously found that beta-subunit of sodium pump was a cancer biomarker and are investigating how this protein is involved in cancer.

Sodium pump consists of two proteins (alpha and beta) that work together to transport potassium into and sodium out of the heart muscle cells. Sodium and calcium are important in the contraction and relaxation of the heart muscle. The changes in the levels of these ions regulate the pumping of the heart, and alterations in these ionic balances lead to congestive heart failure.

Another protein, called the sodium calcium exchanger, transports sodium into and calcium out of the cells. The sodium that enters the cells is “pumped” out by sodium pump. Therefore, the contraction and relaxation of the heart is regulated by the teamwork of sodium pump and sodium calcium exchanger.

Digitalis has been used to treat congestive heart failure for several decades. This drug binds to the alpha protein of the sodium pump and temporarily stops its function, resulting in an accumulation of sodium inside the heart muscle cells. When sodium builds up, it stops the sodium calcium exchanger. This results in increased calcium levels in the cells, which leads to the contraction of the heart.

“For decades it was believed that the alpha protein of sodium pump is the major player in the regulation of cardiac muscle contraction. We have now shown that the beta protein plays a critical role in regulating the function of sodium calcium exchanger and contraction of the heart,” says Dr. Rajasekaran.

The first author of this study Dr. Sonali Barwe, a junior faculty at NCCCR, studied genetically engineered mice to show that reduced sodium pump beta protein predisposes the heart to a condition that it is incapable of enduring stress and insensitive to drugs similar to digitalis.

“This is an intriguing and an unexpected finding, which should open new understanding on cardiac function,” said Dr. Kenneth Roos, Professor of Physiology at UCLA and a collaborator on this study.

This research suggests that reduced expression of beta protein might prognosticate potential cardiac malfunction in the human heart.

This study was supported by funds from NIH DK56216 and Nemours Foundation.

About the Nemours Center for Childhood Cancer Research

The Nemours Center for Childhood Cancer Research is research entity of Nemours Biomedical Research at the Alfred I. duPont Hospital for Children. The NCCCR is located in a fully renovated laboratory space in 1701 Rockland Road, Wilmington, DE. The goal of the center is to evolve into a leader in research focusing on discovery of new drugs and biomarkers for childhood cancers and reduce side effects arising due to cancer treatment in children. The NCCCR will work closely with the University of Delaware, Helen F. Graham Cancer Center, Delaware Biotechnology Institute and the Thomas Jefferson University. For more information, please visit Nemours Center for Childhood Cancer Research.