Researchers solve puzzle of proteins linked to heart failure

February 22, 2012

Sudden cardiac death is a risk for patients with heart failure because the calcium inside their heart cells is not properly controlled and this can lead to an irregular heartbeat. New findings published in PLoS ONE, which reveal mechanisms that underlie this life-threatening risk, provide new possibilities for fighting it.

The study, led by researchers from the University of Bristol's School of Physiology and Pharmacology, show how two individual but very similar proteins cooperatively adjust the amount of calcium inside the heart cells, and how this dual regulation may degenerate in .

In the heart cells of healthy people, calcium is released from intracellular stores and causes the heart to beat strongly so that it can pump blood around the body. The intracellular stores of calcium are released through specialised gates called 'ryanodine receptor (RyR) channels' in a controlled manner at appropriate times and in suitable quantities. In , release of intracellular calcium can become irregular and less tightly controlled resulting in an .

By removing individual RyR channels from and incorporating them into artificial membranes, the researchers were able to measure the tiny calcium currents that flow through a single channel molecule.

The team discovered that two individual proteins, called FKBP12 and FKBP12.6, bind tightly to the RyR channels and alter the amount of calcium that flows through them.

Their study shows that although FKBP12 and FKBP12.6 are almost identical, the proteins have very different functions. FKBP12 increases calcium fluxes through RyR channels while FKBP12.6 blocks the effects of FKBP12. It seems that this dual regulation by the two proteins may be damaged in heart failure.

Dr Rebecca Sitsapesan at the University, said: "Diseases of the heart and circulatory systems are the main cause of death in the UK and account for almost 191,000 deaths each year — one in three deaths1. These new findings are important because we can use this information to help develop new treatments for patients with heart disease to reduce the risks of ."

More information: 'FKBP12 activates the cardiac ryanodine receptor Ca2+-release channel and is antagonised by FKBP12.6', by E. Galfré, S. J. Pitt, E. Venturi, M. Sitsapesan, N.R. Zaccai, K. Tsaneva-Atanasova, S. O'Neill and R. Sitsapesan is published in PLoS ONE [21 February 2012].

Related Stories

Recommended for you

Researchers develop new method to generate human antibodies

July 24, 2017
An international team of scientists has developed a method to rapidly produce specific human antibodies in the laboratory. The technique, which will be described in a paper to be published July 24 in The Journal of Experimental ...

A sodium surprise: Engineers find unexpected result during cardiac research

July 20, 2017
Irregular heartbeat—or arrhythmia—can have sudden and often fatal consequences. A biomedical engineering team at Washington University in St. Louis examining molecular behavior in cardiac tissue recently made a surprising ...

Want to win at sports? Take a cue from these mighty mice

July 20, 2017
As student athletes hit training fields this summer to gain the competitive edge, a new study shows how the experiences of a tiny mouse can put them on the path to winning.

'Smart' robot technology could give stroke rehab a boost

July 19, 2017
Scientists say they have developed a "smart" robotic harness that might make it easier for people to learn to walk again after a stroke or spinal cord injury.

Engineered liver tissue expands after transplant

July 19, 2017
Many diseases, including cirrhosis and hepatitis, can lead to liver failure. More than 17,000 Americans suffering from these diseases are now waiting for liver transplants, but significantly fewer livers are available.

Lunatic Fringe gene plays key role in the renewable brain

July 19, 2017
The discovery that the brain can generate new cells - about 700 new neurons each day - has triggered investigations to uncover how this process is regulated. Researchers at Baylor College of Medicine and Jan and Dan Duncan ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.