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 Why might reading make myopic?
18.07.2018 | Universitätsklinikum Tübingen

nachricht Unique brain 'fingerprint' can predict drug effectiveness
11.07.2018 | McGill University

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: First evidence on the source of extragalactic particles

For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.

To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.

Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...

Im Focus: Breaking the bond: To take part or not?

Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.

A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...

Im Focus: New 2D Spectroscopy Methods

Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.

"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....

Im Focus: Chemical reactions in the light of ultrashort X-ray pulses from free-electron lasers

Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.

Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

Scientists uncover the role of a protein in production & survival of myelin-forming cells

19.07.2018 | Life Sciences

In the ocean's twilight zone, tiny organisms may have giant effect on Earth's carbon cycle

19.07.2018 | Earth Sciences

Lying in a foreign language is easier

19.07.2018 | Social Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>