Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Molecular defect found that may cause heart failure

20.09.2005


A new study has identified a molecular defect in cardiac cells that may be a fundamental cause of heart failure, a progressive weakening of the heart that leaves the organ unable to pump blood through the body.

The findings, by researchers at the Ohio State University Dorothy M. Davis Heart and Lung Research Institute, show that specialized proteins called ryanodine receptors (RyRs) malfunction in the failing heart. The RyRs form channels that become leaky, leading to calcium imbalances that prevent the heart from contracting effectively and relaxing adequately. The condition worsens until the heart can no longer work as a pump.

The root causes of heart failure are not known.



“We found some drastic changes in the way muscle cells in the failing heart handle calcium,” says principal investigator Sandor Gyorke, professor of physiology and cell biology at the OSU Davis Heart and Lung Research Institute. “Discovery of this mechanism suggests at least one potential target for treating the causes of this disease in a rational manner.”

Currently, the only way to correct heart failure is by heart transplantation.

About 4.9 million Americans are currently living with heart failure, and an estimated 265,000 of them die of it yearly. Those with the condition are at six to nine times greater risk of experiencing sudden cardiac death than someone in the general population. From 1992 to 2002, deaths from heart failure rose 35 percent and the incidence is expected to keep rising.

Calcium plays a fundamental role in muscle contraction, particularly in heart muscle. A heart contraction begins when the heart’s pacemaker sends an electrical signal to heart-muscle cells. The electrical signal triggers the release of calcium from a large storage site within each muscle cell. The released calcium activates the muscle cell’s contractile machinery, which causes the cell, and the heart as a whole, to contract.

This calcium storage site is known as the sarcoplasmic reticulum (SR), and it resembles a convoluted, flattened sack within the cell. The delicate, membrane-bound walls of the SR are penetrated with thousands of RyR channels. These serve as gate keepers that allow calcium to flood into the cell to initiate contraction.

The amount of calcium stored in the SR determines the strength of the heart beat and how much blood the heart ejects when it contracts.

At the end of a contraction, the channels close tightly. Molecular pumps, also located in the walls of the SR, then suck the released calcium back into the SR to prepare for the next contraction.

For this study, the OSU investigators used microscopic fluorescence imaging techniques to monitor changes in calcium ion concentrations in the SR and other regions of individual isolated heart cells.

They found that in heart failure, the channels cannot close tightly after a contraction. Instead, they remain partly open throughout the cardiac cycle. This allows some of the calcium to leak out.

This leaves too little calcium in the SR, so strong contrations are not possible, and too much calcium outside SR, so the muscle cells remain slightly contracted and the heart cannot fully relax.

As the condition worsens, the heart grows weaker as a pump.

Gyorke and his colleagues are now working to better understand the damage to the RyR channel.

Funding from the National Heart, Lung and Blood Institute; the American Heart Association; and the OSU Research Foundation supported this research.

Darrell E. Ward | EurekAlert!
Further information:
http://www.osu.edu

More articles from Life Sciences:

nachricht Cryo-electron microscopy achieves unprecedented resolution using new computational methods
24.03.2017 | DOE/Lawrence Berkeley National Laboratory

nachricht How cheetahs stay fit and healthy
24.03.2017 | Forschungsverbund Berlin e.V.

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

Im Focus: Researchers Imitate Molecular Crowding in Cells

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Argon is not the 'dope' for metallic hydrogen

24.03.2017 | Materials Sciences

Astronomers find unexpected, dust-obscured star formation in distant galaxy

24.03.2017 | Physics and Astronomy

Gravitational wave kicks monster black hole out of galactic core

24.03.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>