Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

UT Southwestern researchers reveal mechanisms of smooth-muscle contraction

06.04.2004


Researchers at UT Southwestern Medical Center at Dallas are the first to use genetically engineered mice containing a fluorescent molecule to examine in real time the chemical reactions that result in smooth-muscle contraction.


UT Southwestern’s Dr. Kristine Kamm (left), associate professor of physiology, Dr. Yusuke Mizuno, postdoctoral researcher, and Dr. James Stull, chairman of physiology, analyze data from recent experiments investigating how smooth-muscle cells contract.



Smooth muscle, found in the walls of blood vessels and in internal organs such as lungs, stomach and the bladder, contracts as the end result of a series of chemical reactions. In a new study, UT Southwestern researchers report that one set of chemical reactions resulting in the contraction of the smooth-muscle cells is augmented by a second chemical pathway that kicks in when the first pathway is limited.

"Understanding the underlying chemical signals involved in this process may have implications in treating conditions such as hypertension and other smooth muscle related conditions where there is too much contractile activity," said Dr. James Stull, chairman of physiology at UT Southwestern and senior author of the study.


The research appears in an upcoming issue of the Proceedings of the National Academy of Sciences and was to be posted online this week.

Dr. Stull and his colleagues discovered that when one of the chemicals in the primary contraction mechanism – a protein called calmodulin – is in short supply, a second series of chemical reactions kicks in to take up the slack. The result is that the strength of the contraction of smooth-muscle cells remains robust.

The first step in the primary chemical pathway for muscle contraction is for calcium in the muscle cell to combine with calmodulin. Then, the calcium/calmodulin complex "activates" a protein called myosin light chain kinase (MLCK). If not activated, MLCK cannot transfer phosphate to the motor protein myosin. Myosin needs the phosphate – in a process called phosphorylation – to initiate contraction in smooth-muscle cells.

When the researchers treated smooth muscle cells from mice with the drug carbachol, the amount of calcium available within the cells increased. Because there is much more calmodulin than MLCK in cells, they expected the increase in calcium to lead to more MLCK activation, and that therefore the contraction would be stronger.

The researchers saw the strong muscle contraction, but they only saw a small increase in MLCK activation, not enough to account for the muscle response. They discovered that because MLCK was competing for calmodulin with other calmodulin-binding proteins, there was only enough calmodulin available in this system to activate a small portion of the MLCK.

"Surprisingly, there is not enough calmodulin for all of its targets," Dr. Stull said. "So the signaling system has recruited a second pathway to enhance the limited activation of MLCK, which leads to a strong muscle contraction."

At the end of the primary chemical pathway, an enzyme called phosphatase can remove the phosphate from the myosin, hampering the muscle cell contraction. But the second chemical pathway inhibits the phosphatase from removing the phosphate.

"In this second pathway, the phosphates are no longer taken away from the myosin, which allows more phosphorylated myosin to remain, leading to a stronger muscle contraction," Dr. Stull said.

To track the progress of this intricate chemical dance, researchers genetically engineered a mouse containing a fluorescent molecule, or biosensor that directly monitors the calcium/calmodulin activation of MLCK in real time in smooth-muscle cells.

"These studies demonstrate the feasibility of producing transgenic biosensor mice for investigations of signaling processes in intact systems," Dr. Stull said.


Other UT Southwestern researchers involved in the study were Dr. Kristine Kamm, associate professor of physiology and a longtime collaborator for studies on muscle; Drs. Kim Lau and Gang Zhi, assistant professors of physiology; and postdoctoral researchers Drs. Eiji Isotani, Jian Huang, Yusuke Mizuno and Ramaz Geguchadze. Dr. Anthony Persechini from the University of Missouri-Kansas City also contributed. The research was supported by the National Institutes of Health and the Moss Heart Fund.

To automatically receive news releases from UT Southwestern via e-mail, subscribe at http://www.utsouthwestern.edu/utsw/cda/dept37326/files/37813.html

Amanda Siegfried | UT Southwestern
Further information:
http://www.utsouthwestern.edu/utsw/cda/dept37389/files/161304.html
http://www.utsouthwestern.edu/utsw/cda/dept37326/files/37813.html

More articles from Life Sciences:

nachricht Researchers identify potentially druggable mutant p53 proteins that promote cancer growth
09.12.2016 | Cold Spring Harbor Laboratory

nachricht Plant-based substance boosts eyelash growth
09.12.2016 | Fraunhofer-Institut für Angewandte Polymerforschung IAP

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Electron highway inside crystal

Physicists of the University of Würzburg have made an astonishing discovery in a specific type of topological insulators. The effect is due to the structure of the materials used. The researchers have now published their work in the journal Science.

Topological insulators are currently the hot topic in physics according to the newspaper Neue Zürcher Zeitung. Only a few weeks ago, their importance was...

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

Researchers identify potentially druggable mutant p53 proteins that promote cancer growth

09.12.2016 | Life Sciences

Scientists produce a new roadmap for guiding development & conservation in the Amazon

09.12.2016 | Ecology, The Environment and Conservation

Satellites, airport visibility readings shed light on troops' exposure to air pollution

09.12.2016 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>