Type A and can't handle it?

September 27, 2002

ROCHESTER, Minn. -- Mayo Clinic researchers today identified a genetic basis for the heart's ability to withstand fight-or-flight responses: a protein called Kir6.2 enables the heart to react to stress without distress.

Mice lacking this key protein had reduced cardiac tolerance for both exercise- and adrenaline-like stress. Nearly three-quarters (73 percent) of the Kir6.2-deficient mice died within 14 minutes after a stressor challenged their cardiac response -- yet all the mice that possessed Kir6.2 survived the stress tests.

As reported in the Oct. 1 edition of Proceedings of the National Academy of Sciences, the research provides provocative leads to understanding and treating stress-related disorders of the heart. These may range from sudden death of highly conditioned athletes to the cumulative effects of psychological stress at work, school or in family life.

"We have identified in the heart a protective mechanism against stress that is roughly analogous to an automatic sprinkler system that douses a fire in an emergency," says Andre Terzic, M.D., Ph.D, lead researcher. "The Kir6.2 protein senses stress and prevents damage to the heart by helping the cells maintain equilibrium even under peak workloads. Lack of Kir6.2 protein function causes sudden, irreversible damage to heart cells, which could lead to heart failure."

In the study, the Mayo Clinic team led by Dr. Terzic compared mice in which the gene that produces the Kir6.2 protein had been eliminated to a control group of mice that possessed the Kir6.2 protein. Their goal was to determine whether Kir6.2 enables heart cells to maintain high levels of activity without suffering damage, and to discover how it works.

Study Findings

In treadmill testing, the normal mice tolerated more than three times the workload that the Kir6.2-deficient mice could. Both groups of mice were also tested under stress induced by a compound similar in effect to adrenaline, the body's natural fight-or-flight hormone. In mice lacking Kir6.2, hearts did not contract as completely under stress -- and 73 percent developed severe heart rhythm disturbances called arrhythmias, then died suddenly.

By contrast, none of the normal mice experienced a fatal arrhythmia.

Study Significance

Kir6.2, a protein common to all animals, is at the core of the KATP channel complex that choreographs an intricate chemical dance between potassium and calcium flow in the heart. By conducting potassium, the KATP channel enables the cells to more quickly restore electrical balance following each heartbeat, thus limiting the entrance of calcium into the cells.

"The system needs to be fully orchestrated," says Dr. Terzic. "It must have perfect harmonization to bring sufficient calcium for contraction without overdoing it." When the orchestra is "off tempo," the chemical dancers are out of step. The result: cardiac distress under stress.

The Mayo Clinic study found that heart cells in the mice lacking Kir6.2 overloaded with calcium -- and this damaged cell structure. Administering calcium-channel blockers, a common heart medication, to those Kir6.2-deficient mice prevented the fatal arrhythmias in five out of six.

Thus, the Mayo Clinic study shows that Kir6.2 is crucial to survival under the sudden rush of cardiac output required by the flight-or-fight response of the sympathetic nervous system to threats -- be they from a saber tooth cat or a bear market. "Because of the selective advantage it confers, Kir6.2 has been maintained through evolution in the gene package of many organisms," explains Dr. Terzic.

The next steps for the Mayo Clinic researchers will be developing the diagnostic and therapeutic potential of these findings. A blood test could identify individuals who are deficient in KATP channel proteins, or whose supporting protein-signaling system isn't working, and drug or gene therapies could compensate for those deficiencies. "Understanding that this protein is so important, we can now work on ways to repair it when defective within the cells, or to boost its ability to respond," Dr. Terzic concludes.
Additional Contact information for Lee Aase: 507-284-2511 (evenings)

Mayo Clinic

Related Stress Articles from Brightsurf:

Stress-free gel
Researchers at The University of Tokyo studied a new mechanism of gelation using colloidal particles.

Early life stress is associated with youth-onset depression for some types of stress but not others
Examining the association between eight different types of early life stress (ELS) and youth-onset depression, a study in JAACAP, published by Elsevier, reports that individuals exposed to ELS were more likely to develop a major depressive disorder (MDD) in childhood or adolescence than individuals who had not been exposed to ELS.

Red light for stress
Researchers from the Institute of Industrial Science at The University of Tokyo have created a biphasic luminescent material that changes color when exposed to mechanical stress.

How do our cells respond to stress?
Molecular biologists reverse-engineer a complex cellular structure that is associated with neurodegenerative diseases such as ALS

How stress remodels the brain
Stress restructures the brain by halting the production of crucial ion channel proteins, according to research in mice recently published in JNeurosci.

Why stress doesn't always cause depression
Rats susceptible to anhedonia, a core symptom of depression, possess more serotonin neurons after being exposed to chronic stress, but the effect can be reversed through amygdala activation, according to new research in JNeurosci.

How plants handle stress
Plants get stressed too. Drought or too much salt disrupt their physiology.

Stress in the powerhouse of the cell
University of Freiburg researchers discover a new principle -- how cells protect themselves from mitochondrial defects.

Measuring stress around cells
Tissues and organs in the human body are shaped through forces generated by cells, that push and pull, to ''sculpt'' biological structures.

Cellular stress at the movies
For the first time, biological imaging experts have used a custom fluorescence microscope and a novel antibody tagging tool to watch living cells undergoing stress.

Read More: Stress News and Stress Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.