Researchers illuminate link between sodium, calcium and heartbeat

February 13, 2012

Using the Canadian Light Source synchrotron, researchers from the University of British Columbia have revealed, for the first time, one of the molecular mechanisms that regulates the beating of heart cells by controlling the movement of sodium in out of the cells -- and what calcium has to do with it. Their findings are published in the Feb. 14, 2012 issue of the Proceedings of the National Academy of Sciences.

That flutter in your may have more to do with the movement of than the glance of a certain someone across a crowded room.

Using the Canadian Light Source synchrotron, researchers from the University of British Columbia have revealed, for the first time, one of the that regulates the beating of by controlling the movement of in out of the – and what has to do with it. The findings, published February 14 in the , sheds new light on this crucial physiological process while revealing the root cause and possible treatment targets of two potentially life-threatening cardiac arrhythmia conditions.

The contraction and relaxation of heart muscle cells depend on minute but finely regulated electrical impulses that are created when charged atoms – or ions – of metals such as sodium, potassium and calcium pass through complex molecular channels inside and between cells. Irregular heartbeats, referred to medically as arrhythmias, can happen when these channels leak or otherwise malfunction. Professors Filip van Petegem and Christopher Ahern, members of UBC's Cardiovascular Research Group, used the CLS to determine the molecular structure of a part of the channel that controls the flow of sodium to cells in the heart, as well as in other electrically-excitable cells such as in the nervous system.

"The heart is an electrical organ that depends on precise electrical signals to contract [and pump blood]" explains van Petegem. "It is crucial for heart rate that the signalling, controlled by the movement of sodium, be exact. So the entry of sodium into the cell is tightly regulated."

The that passes through the outer membrane of heart cells is actually a huge, intertwined four-part molecule. The teams of Van Petegem and Ahern chose a section of the molecule that appeared to regulate the closing of the channel by forming a plug, thus stopping sodium from getting through.

The researchers were surprised to discover that a protein called calmodulin binds to the sodium channel, keeping it open by preventing the plug from forming. Calcium ions, in turn, regulate the connection between the protein and the channel: calcium ions cause the protein to hook up to the channel, keeping it open and letting sodium through.

Problems occur with the system when genetic mutations change the shape of the channel at the site where the protein binds, affecting how well the channel can open and close. The result – the flow of sodium into the muscle cells is disrupted and the heart does not beat regularly.

The scientists have been able to identify mutations in the site that lead to two different kinds of heart arrhythmia: Brugada Syndrome and Long Q-T type 3, so-called from the tell-tale trace doctors see on the ECG of patients suffering from the problem. Brugada syndrome is considered to be caused by not enough sodium getting into cells, while long Q-T is the result of too much sodium.

The results of the study could pave the way for the development of new drugs that can shore up how the calmodulin protein binds to the sodium channel, effectively treating both conditions as well as other arrhythmias.

"It's really a very elegant mechanism," notes van Petegem. "Many channels are regulated by calmodulin but not in such a simple way."

Explore further: Atomic structure discovered for a sodium channel that generates electrical signals in living cells

Related Stories

Atomic structure discovered for a sodium channel that generates electrical signals in living cells

July 13, 2011
Scientists at the University of Washington (UW) in Seattle have determined the atomic architecture of a sodium channel. The achievement opens new possibilities for molecular medicine researchers around the world in designing ...

Molecular mechanism for some anti-arrhythmia drugs discovered

June 14, 2011
University of British Columbia researchers – using an innovative, atom-by-atom substitution method – have uncovered the mechanism by which a particular class of drugs controls irregular heartbeats.

Recommended for you

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.

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 ...

'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.

New animal models for hepatitis C could pave the way for a vaccine

July 19, 2017
They say that an ounce of prevention is worth a pound of cure. In the case of hepatitis C—a disease that affects nearly 71 million people worldwide, causing cirrhosis and liver cancer if left untreated—it might be worth ...

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.