By contrast, none of the normal mice experienced a fatal arrhythmia.
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
Contact: Lee Aase