Are cold feet plaguing your relationship? Physiologists identified biological mechanism that could be responsible

July 31, 2012

Cold feet -- those chilly appendages that plague many people in the winter and an unlucky few all year round -- can be the bane of existence for singles and couples alike. In a new study, scientists led by Selvi C. Jeyaraj of the Research Institute at Nationwide Children's Hospital have identified a biological mechanism that may be responsible for icy extremities: an interaction between a series of molecules and receptors on smooth muscle cells that line the skin's tiny blood vessels.

The new research, along with an accompanying editorial by Martin C. Michel of Johannes Gutenberg University in Mainz, Germany, and Paul A. Insel of the University of California at San Diego, suggest new contributors to this near-universal problem and potential targets to treat more serious problems that affect blood vessels in the cold, such as in Raynaud's disease.

The article, entitled "Cyclic AMP-Rap1A Signaling Activates RhoA to Induce a2C-Adrenoceptor Translocation to the of Microvascular " (http://bit.ly/N8ZzKh), appears in the Articles in PresS section of the – Cell Physiology (http://ajpcell.physiology.org/) published by the American Physiological Society. The accompanying editorial, "Can You Blame Cold Feet on Epac (and Rap1A)? Focus on "Cyclic AMP-Rap1A Signaling Activates RhoA to Induce α2C-adrenoceptor to the Cell Surface of Microvascular Cells," is also online (http://bit.ly/LYDXFd).

Methodology

Jeyaraj and her colleagues studied smooth derived from tiny blood vessels harvested from human skin biopsies and similar cells from mouse tail arteries. These cells contain receptors known as a2C-AR, which cause constriction in their associated blood vessels and shut off blood flow under chilly conditions to conserve heat. The scientists also worked with different cells, called HEK cells, that do not normally express a2C-AR but that can be modified to do so. Also studied were cells taken from tail arteries of mice genetically altered to no longer express a protein called Rap1A, which the authors hypothesized would interact with a2C-AR.

Results

The researchers found that when they dosed cells that expressed a2C-AR with chemicals that activate Rap1A, either directly or through means that involve another protein called Epac, the drew from pools of a2C-AR near the cell's nucleus and moved these to the cell surface. The series of events involved rearrangment of the cell's internal "skeleton," fibers that determine its shape and can transport items from one area of a cell to another.

Importance of the Findings and What Part of Cell Physiology Gets 'The Rap'

Authors of the study and the accompanying editorial suggest that the series of events and biological interactions they identified could be responsible for the mechanism the body uses to limit blood supply to the skin in cold temperatures, which conserves more blood flow—and hence, warmth—for the body's internal organs. The findings may provide clues to where dysfunction occurs in disorders in which blood flow is erroneously cut off, such as Raynaud's disease. In this condition, sufferers lose circulation to the fingers, toes, and occasionally other areas when the body overreacts to cold temperatures. Raynaud's can sometimes be serious, leading to atrophy of skin and muscle, ulceration and rarely to ischemic gangrene. On a lighter note, the results also provide a possible explanation for the age-old problem of cold feet.

"Thus, if your partner complains again about your cold feet," the editorial authors write, "you have some new excuses: 'It's Epac's fault!' or 'Rap1A should get the rap!'"

Study Team

In addition to Selvi C. Jeyaraj, the study team also includes Nicholas T. Unger and N. Paul El-Dahdah of The Research Institute at Nationwide Children's Hospital, Ali H. Eid of Qatar University, Srabani Mitra of Ohio State University, Lawrence A. Quilliam of Indiana University School of Medicine, Nicholas A. Flavahan of Johns Hopkins University, and Maqsood A. Chotani of The Research Institute at Nationwide Children's Hospital and Ohio State University.

Explore further: Cambridge team first to grow smooth muscle cells from patient skin cells

Related Stories

Cambridge team first to grow smooth muscle cells from patient skin cells

January 26, 2012
A Cambridge University research team has for the first time discovered a method of generating different types of vascular smooth muscle cells (SMCs) - the cells which make up the walls of blood vessels - using cells from ...

New findings may help explain high blood pressure in pregnancy

October 31, 2011
Virginia Commonwealth University School of Medicine researchers have discovered that the infiltration of white blood cells into an expectant mother's blood vessels may explain high blood pressure in pregnancy.

Recommended for you

Estrogen discovery could shed new light on fertility problems

December 12, 2017
Estrogen produced in the brain is necessary for ovulation in monkeys, according to researchers at the University of Wisconsin-Madison who have upended the traditional understanding of the hormonal cascade that leads to release ...

Time of day affects severity of autoimmune disease

December 12, 2017
Insights into how the body clock and time of day influence immune responses are revealed today in a study published in leading international journal Nature Communications. Understanding the effect of the interplay between ...

3-D printed microfibers could provide structure for artificially grown body parts

December 12, 2017
Much as a frame provides structural support for a house and the chassis provides strength and shape for a car, a team of Penn State engineers believe they have a way to create the structural framework for growing living tissue ...

Potassium is critical to circadian rhythms in human red blood cells

December 12, 2017
An innovative new study from the University of Surrey and Cambridge's MRC Laboratory of Molecular Biology, published in the prestigious journal Nature Communications, has uncovered the secrets of the circadian rhythms in ...

Team identifies DNA element that may cause rare movement disorder

December 11, 2017
A team of Massachusetts General Hospital (MGH) researchers has identified a specific genetic change that may be the cause of a rare but severe neurological disorder called X-linked dystonia parkinsonism (XDP). Occurring only ...

Protein Daple coordinates single-cell and organ-wide directionality in the inner ear

December 11, 2017
Humans inherited the capacity to hear sounds thanks to structures that evolved millions of years ago. Sensory "hair cells" in the inner ear have the amazing ability to convert sound waves into electrical signals and transmit ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.