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 Usher syndrome: Gene therapy restores hearing and balance
25.09.2017 | Institut Pasteur

nachricht MRI contrast agent locates and distinguishes aggressive from slow-growing breast cancer
25.09.2017 | Case Western Reserve 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: The fastest light-driven current source

Controlling electronic current is essential to modern electronics, as data and signals are transferred by streams of electrons which are controlled at high speed. Demands on transmission speeds are also increasing as technology develops. Scientists from the Chair of Laser Physics and the Chair of Applied Physics at Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) have succeeded in switching on a current with a desired direction in graphene using a single laser pulse within a femtosecond ¬¬ – a femtosecond corresponds to the millionth part of a billionth of a second. This is more than a thousand times faster compared to the most efficient transistors today.

Graphene is up to the job

Im Focus: LaserTAB: More efficient and precise contacts thanks to human-robot collaboration

At the productronica trade fair in Munich this November, the Fraunhofer Institute for Laser Technology ILT will be presenting Laser-Based Tape-Automated Bonding, LaserTAB for short. The experts from Aachen will be demonstrating how new battery cells and power electronics can be micro-welded more efficiently and precisely than ever before thanks to new optics and robot support.

Fraunhofer ILT from Aachen relies on a clever combination of robotics and a laser scanner with new optics as well as process monitoring, which it has developed...

Im Focus: The pyrenoid is a carbon-fixing liquid droplet

Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.

A warming planet

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Nerves control the body’s bacterial community

26.09.2017 | Life Sciences

Four elements make 2-D optical platform

26.09.2017 | Physics and Astronomy

Goodbye, login. Hello, heart scan

26.09.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>