Scientists studying heart cells have devised a new way to visualize and quantify the rise and fall in the activity of a key enzyme linked to heart failure, offering them a window to the inner workings of heart cells that is expected to help in the development of more effective drugs to treat heart failure.
In a paper to appear in the Aug. 7 online edition of Proceedings of the National Academy of Sciences, the researchers at the University of California, San Diego describe the use of an engineered protein partly derived from a jelly fish that fluoresces within heart cells in tandem with activation of the key enzyme called PKA (protein kinase A). By combining computer modeling with the novel fluorescence-imaging technique in living cells, the researchers were able to uncover new details in the molecular control of PKA.
PKA is an intensely studied regulatory enzyme whose activity in heart cells rises sharply in response to exercise or various stresses, priming the heart to beat faster and with more power, and to increase its metabolic rate to meet the increased energy demands.
"For the first time, this innovative visualization technique allowed us to refine our computational models get a better understanding of the interacting biochemical pathways in heart cells that involve PKA," said Andrew McCulloch, a professor and chair of the Department of Bioengineering at UCSD's Jacobs School of Engineering. "Now we're in a good position to do similar experiments with mutant strains of mice that experience heart failure in ways that mimic human disease."
McCulloch is an expert at mathematical modeling the interactions of hundreds of enzymes and other molecules in heart cells. McCulloch and a team of Ph.D. candidates in bioengineering, including recent graduate Jeffrey Saucerman, collaborated with another group at UCSD led by Roger Y. Tsien, a professor of medicine, pharmacology, and chemistry and biochemistry and a Howard Hughes M
Contact: Rex Graham
University of California - San Diego