Researchers at the University of Rochester Medical Center have created a new method to test the activity of mitochondrial ATP-sensitive potassium channel (mK ATP) and identified a molecule, phosphatidyilnositol-4, 5- bisphosphate (PIP 2), that holds the ability to restore heart activity once it has stopped, according to research published in the Feb. 25 issue of Circulation Research.
Paul S. Brookes, PhD, and colleagues evaluated why ischemic preconditioning can strengthen cardiac tissue and aid people previously stricken with a heart attack compared to those who have no preconditioning.
To measure the activity of mK ATP, Brookes and colleagues developed a thallium-sensitive (TI +) fluorophore molecule. According to researchers, “The new method involves measuring the movement of the element thallium into and out of mitochondria, as a surrogate for potassium.”
The researchers found the following:
- Development of a novel TI + flux based assay for the mK ATP channel;
- Time-dependent loss of mK ATP channel activity is a genuine run-down phenomenon and is reversed by PIP 2; and
- FLX blocks both mK ATP channel activity and IPC-mediated cardioprotection.
“Collectively, the data support the concept that mK ATP contains a bona fide K IR channel,” the authors wrote.
According to the researchers, the TI + flux are “superior to those of the swelling based assay.” They found that fluorescence is attained within two to four seconds, compared to that of osmotic swelling assay, which takes 20 to 30 seconds.
"Preconditioning has been shown to be effective in a variety of models in the laboratory, but it hasn't made it to the clinic yet,” said Brookes. "One would want to design a drug to get the benefit of ischemic preconditioning without actually impeding blood flow in any way."
Brooke and colleagues found during the research that mK ATP is inhibited by the drug fluoxetine (Prozac; Eli Lilly) and had been shown to hamper ischemic preconditioning.
“Because medications like anti-depressants and beta-blockers are used so widely in patients who have had heart problems, scientists should take a close look at their possible effects on ischemic preconditioning,” Brookes said.
The authors urged that FLX be added to the most commonly prescribed medications list. In addition, Brookes and colleagues found that lithium is known to increased cardiac PIP 2 levels and induce cardioprotection.
The study was funded by the American Heart Association.