Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Calcium channels control coronary artery relaxation

21.11.2003


Researchers have discovered that a specific type of calcium channel -- a pore-like protein that nestles in the cell membrane and controls the flow of calcium into the cell -- regulates the relaxation of coronary arteries.



The studies showed that mice engineered to lack these calcium channels had constricted coronary arteries and had fibrous tissue in their hearts, which was evident when the animals’ hearts reacted to chronic blood restriction. The researchers hypothesize that drugs targeting this calcium channel might one day be used to treat cardiovascular disease by opening arteries.

The researchers, led by Howard Hughes Medical Institute investigator Kevin Campbell, published their findings in the November 21, 2003, issue of the journal Science. Campbell and his colleagues at the University of Iowa collaborated with researchers from the Veterans Administration Medical Center in Iowa City, Loyola University Medical Center and the University of Texas Southwestern Medical Center.


The calcium channel under study is triggered by voltage differences across the cell membrane that cause it to open and allow calcium to flow into the cell. The operation of calcium channels is crucial to a wide array of physiological functions, including transmission of nerve impulses, muscle contraction and activation of genes. Although one type of calcium channel, called the L-type, had been shown to control muscle contraction, the action of the other type, called the T-type, remained largely unknown, said Campbell. The L-channel opens in response to large voltage differences across the cell membrane, while the T-channel responds to a weaker "depolarization," he said.

Campbell and his colleagues first became interested in exploring the T-channel because research by other scientists hinted that it might be involved in the fusion of muscle cells, or myoblasts, to one another during the development and repair of muscles. Campbell’s laboratory concentrates on muscular dystrophies, and the scientists reasoned that better understanding of the muscle-formation machinery would aid that effort.

To study the T-channels, the researchers created a knockout mouse lacking one type of T-channel, called the á1H channel. "Although our main interest was initially to look at how the myoblasts would function and fuse, we found that myoblasts looked completely normal in these animals," said Campbell. "We then realized that another type of channel, the á1G, could upregulate to compensate for the loss." However, when the scientists studied the structure of the various muscle tissues, they found a striking accumulation of fibrous tissue in heart muscle.

"We believed that this fibrosis was probably not due directly to the cardiac muscle abnormality, because we knew that a T-channel was not present in adult ventricular muscle," said Campbell. "So, it must have been caused by another abnormality, maybe in the blood vessels."

When the researchers performed visual studies of the coronary arteries of the mice and measured their contractility, they found the arteries to be irregularly shaped and constricted, although the vessels contracted normally. Such aberrations would have starved the heart of blood, inducing fibrosis, said Campbell.

To test the ability of the coronary arteries of the knockout mice to relax, the researchers administered drugs that in wild-type mice caused arterial dilation. However the drugs produced no such effect in the knockout mice.

"So, this impaired relaxation strongly suggested that this channel was involved in arterial relaxation, which was a surprise because calcium channels had been implicated in contraction, but not in relaxation," said Campbell.

Sure enough, when the researchers administered nickel -- which blocks T-channels -- to wild-type mice, dilation of their arteries was decreased.

Other research had shown that an entirely different channel, a potassium channel, plays a key role in regulating muscle relaxation. Campbell and his colleagues theorized that calcium ions flowing through T-channels might somehow "fine-tune" potassium channels.

Findings from two of their experiments supported this idea, said Campbell. A drug that opens potassium channels caused arterial dilation in both wild-type and T-channel knockout mice, they found. Also, when they isolated the potassium channel, they found it to be physically associated with the T-channel.

A great many puzzles remain concerning how the T-channel functions in coronary artery relaxation, said Campbell. One puzzle arises from the scientists’ finding that an artery-relaxing drug, called sodium nitroprusside, produced some arterial relaxation in the knockout mice. This drug releases the artery-relaxing chemical nitric oxide, leading the scientists to believe that only nitric-oxide-mediated relaxation is defective in the knockout mice.

A better understanding of T-channels function could lead to new treatments for cardiovascular disease, said Campbell. "Our current findings indicate that blocking this channel causes coronary artery constriction, which is clearly something you don’t want to do in treating heart disease," said Campbell. "However, if drugs could be developed that would open the channel, it might lead to relaxation and opening of the arteries. There are currently a number of treatments for opening blood vessels, but it’s possible that understanding this process could lead to new approaches to causing vasorelaxation," he said. "We’re very excited about the potential for this work."

Jim Keeley | EurekAlert!
Further information:
http://www.hhmi.org/

More articles from Life Sciences:

nachricht Overlooked molecular machine in cell nucleus may hold key to treating aggressive leukemia
23.04.2019 | Cincinnati Children's Hospital Medical Center

nachricht Bacteria use their enemy -- phage -- for 'self-recognition'
23.04.2019 | Chinese Academy of Sciences Headquarters

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Quantum gas turns supersolid

Researchers led by Francesca Ferlaino from the University of Innsbruck and the Austrian Academy of Sciences report in Physical Review X on the observation of supersolid behavior in dipolar quantum gases of erbium and dysprosium. In the dysprosium gas these properties are unprecedentedly long-lived. This sets the stage for future investigations into the nature of this exotic phase of matter.

Supersolidity is a paradoxical state where the matter is both crystallized and superfluid. Predicted 50 years ago, such a counter-intuitive phase, featuring...

Im Focus: Explosion on Jupiter-sized star 10 times more powerful than ever seen on our sun

A stellar flare 10 times more powerful than anything seen on our sun has burst from an ultracool star almost the same size as Jupiter

  • Coolest and smallest star to produce a superflare found
  • Star is a tenth of the radius of our Sun
  • Researchers led by University of Warwick could only see...

Im Focus: Quantum simulation more stable than expected

A localization phenomenon boosts the accuracy of solving quantum many-body problems with quantum computers which are otherwise challenging for conventional computers. This brings such digital quantum simulation within reach on quantum devices available today.

Quantum computers promise to solve certain computational problems exponentially faster than any classical machine. “A particularly promising application is the...

Im Focus: Largest, fastest array of microscopic 'traffic cops' for optical communications

The technology could revolutionize how information travels through data centers and artificial intelligence networks

Engineers at the University of California, Berkeley have built a new photonic switch that can control the direction of light passing through optical fibers...

Im Focus: A long-distance relationship in femtoseconds

Physicists observe how electron-hole pairs drift apart at ultrafast speed, but still remain strongly bound.

Modern electronics relies on ultrafast charge motion on ever shorter length scales. Physicists from Regensburg and Gothenburg have now succeeded in resolving a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Revered mathematicians and computer scientists converge with 200 young researchers in Heidelberg!

17.04.2019 | Event News

First dust conference in the Central Asian part of the earth’s dust belt

15.04.2019 | Event News

Fraunhofer FHR at the IEEE Radar Conference 2019 in Boston, USA

09.04.2019 | Event News

 
Latest News

Marine Skin dives deeper for better monitoring

23.04.2019 | Information Technology

Geomagnetic jerks finally reproduced and explained

23.04.2019 | Earth Sciences

Overlooked molecular machine in cell nucleus may hold key to treating aggressive leukemia

23.04.2019 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>