Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists solve chaotic heartbeat mystery

06.02.2003


Fatal, electrical chaos can develop in the hearts of otherwise healthy people who produce a defective accessory protein called ankyrin-B, reports W. Jonathan Lederer of the University of Maryland Biotechnology Institute (UMBI) and collaborators, in the February 6 issue of the scientific journal Nature.



By discovering the molecular and cellular causes of the electrical chaos-known as Long QT Syndrome Type 4, or LQT4-Lederer and collaborators open the door to possible therapies and diagnostics for this and related heart diseases. The work also provides a clue to how important, specific proteins are organized within heart cells.

Several years ago, clinical researchers in France, headed by Denis Escande, discovered an inheritance pattern in members of a family who had been dying suddenly and unexpectedly in the prime of life. Lederer’s team at UMBI and the University of Maryland at Baltimore and researchers at Duke University, headed by Vann Bennett, collaborated with the French by applying state-of-the-art heart physiology tools to mouse heart cells in order to find the cause of the sudden deaths.


Cardiovascular disease, including cardiac arrhythmia and sudden cardiac death and stroke are the leading causes of death worldwide. The term QT in LQT4 and other long QT syndromes refers to a time period, normally about 300 milliseconds (read between points Q and T on an electrocardiogram) when each electrical pulse, or action potential, starts a heart beat. Longer QT periods can signal heart problems.

The researchers discovered that the LQT4 is linked to a genetic defect in humans and in a mutant mouse developed by the Bennett laboratory. The defect is expressed as an inadequate amount of an important adaptor protein called ankyrin-B that is involved in enriching cells with key proteins at specific locations within the cell. Lederer’s group studied the dynamic physiology of single cells in the Bennett mouse.

The reduction or absence of functional ankyrin-B in the cells causes proteins involved in cellular calcium regulation to be inadequate or absent from critical locations within the cell. Cells load up with too much calcium. The change in calcium causes the heart to beat improperly and, in the case of LQT4, chaotically. The electrical chaos that can cause death appears to be triggered by unexpected stress and possibly an increase in adrenaline - as would happen when individuals are startled, says Lederer. Even then, the death-causing electrical chaos is rare.

Humans and animals are afflicted with LQT4 when only one of the two genes for ankyrin-B is defective or absent. When both are absent, the condition is lethal.

However, says Lederer, many individuals survive for a long time with the defect. The rare occurrence of the development of calcium-dependent electrical chaos in the heart means that most individuals have normal heart behavior even when they are afflicted with LQT4.

Finding the defective protein to be ankyrin-B was somewhat of a surprise, says Lederer, a world leader in studies ion channels and calcium sparks in heart cells. "We thought it would make sense if the defective protein were a channel protein. The other long QT syndromes are caused by defects in channel proteins. This is the first example of a cytoskeletal or structural protein causing such an arrhythmia."

Lederer and his team collaborated with other primary investigators from Duke University and the Howard Hughes Institute headed by Vann Bennett and Peter Mohler and with investigators at the French Institute of Health and Medical Research (INSERM) in Nantes, France, headed by Denis Escande. Key local investigators on the Lederer team included S. Guatimosim, L-S. Song and K. Dilly from MBC and T. B. Rogers and W. duBell from the School of Medicine at University of Maryland, Baltimore.


The University of Maryland Biotechnology Institute was mandated by the state of Maryland legislature in 1985 as "a new paradigm of state economic development in biotech-related sciences." With five major research and education centers across Maryland, UMBI is dedicated to advancing the frontiers of biotechnology. The centers are the Center for Advanced Research in Biotechnology in Rockville; Center for Biosystems Research in College Park; and Center of Marine Biotechnology, Medical Biotechnology Center, and the Institute of Human Virology, all in Baltimore.


Steve Berberich | EurekAlert!
Further information:
http://www.umbi.umd.edu/

More articles from Health and Medicine:

nachricht A promising target for kidney fibrosis
21.04.2017 | Brigham and Women's Hospital

nachricht Stem cell transplants: activating signal paths may protect from graft-versus-host disease
20.04.2017 | Technische Universität München

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

7th International Conference on Crystalline Silicon Photovoltaics in Freiburg on April 3-5, 2017

03.04.2017 | Event News

 
Latest News

NASA's Fermi catches gamma-ray flashes from tropical storms

25.04.2017 | Physics and Astronomy

Researchers invent process to make sustainable rubber, plastics

25.04.2017 | Materials Sciences

Transfecting cells gently – the LZH presents a GNOME prototype at the Labvolution 2017

25.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>