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UT Southwestern researchers reveal mechanisms of smooth-muscle contraction

DALLAS April 5, 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.

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 mi
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Contact: Amanda Siegfried
Amanda.siegfried@utsouthwestern.edu
214-648-3404
UT Southwestern Medical Center
5-Apr-2004


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