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 Newly designed molecule binds nitrogen
23.02.2018 | Julius-Maximilians-Universität Würzburg

nachricht Atomic Design by Water
23.02.2018 | Max-Planck-Institut für Eisenforschung GmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Attoseconds break into atomic interior

A newly developed laser technology has enabled physicists in the Laboratory for Attosecond Physics (jointly run by LMU Munich and the Max Planck Institute of Quantum Optics) to generate attosecond bursts of high-energy photons of unprecedented intensity. This has made it possible to observe the interaction of multiple photons in a single such pulse with electrons in the inner orbital shell of an atom.

In order to observe the ultrafast electron motion in the inner shells of atoms with short light pulses, the pulses must not only be ultrashort, but very...

Im Focus: Good vibrations feel the force

A group of researchers led by Andrea Cavalleri at the Max Planck Institute for Structure and Dynamics of Matter (MPSD) in Hamburg has demonstrated a new method enabling precise measurements of the interatomic forces that hold crystalline solids together. The paper Probing the Interatomic Potential of Solids by Strong-Field Nonlinear Phononics, published online in Nature, explains how a terahertz-frequency laser pulse can drive very large deformations of the crystal.

By measuring the highly unusual atomic trajectories under extreme electromagnetic transients, the MPSD group could reconstruct how rigid the atomic bonds are...

Im Focus: Developing reliable quantum computers

International research team makes important step on the path to solving certification problems

Quantum computers may one day solve algorithmic problems which even the biggest supercomputers today can’t manage. But how do you test a quantum computer to...

Im Focus: In best circles: First integrated circuit from self-assembled polymer

For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.

In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...

Im Focus: Demonstration of a single molecule piezoelectric effect

Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale

Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

2nd International Conference on High Temperature Shape Memory Alloys (HTSMAs)

15.02.2018 | Event News

Aachen DC Grid Summit 2018

13.02.2018 | Event News

How Global Climate Policy Can Learn from the Energy Transition

12.02.2018 | Event News

 
Latest News

Basque researchers turn light upside down

23.02.2018 | Physics and Astronomy

Finnish research group discovers a new immune system regulator

23.02.2018 | Health and Medicine

Attoseconds break into atomic interior

23.02.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>