To see the workings of the cells, Kotlikoff says, “We anesthetize the mouse, ventilate it, open up the chest, and shine light right on the heart.” A group led by Guy Salama at the University of Pittsburgh School of Medicine was responsible for producing movies of the beating hearts. Salama uses a high-speed camera to create clear, high-resolution images. He recorded a frame every millisecond, capturing several images of each heartbeat.
Because the researchers filmed the mice’s hearts at all stages of development, from day-old embryos to adulthood, the movies “show you what’s going on every time the mouse’s heart beats for its whole life,” Kotlikoff says.
In all mammals the heart is the first organ to start working, driven by the embryo’s need for oxygen. However, it has to start pumping before the structures that maintain the heartbeat’s steady pace have developed. Kotlikoff discovered a signalling pathway that helps the embryonic heart maintain its pace for only a few days, until the adult structure develops. He says he has also seen arrhythmias – disruptions in the heart’s steady electrical signals that lead to fast, slow, or erratic heartbeats, and that can cause sudden death.
Kotlikoff says he is breeding mice that make the new fluorescent protein only in specialized heart tissues and parts of the body where calcium is important, such as the brain, where calcium plays an important role in signalling. “We can put it where we want and listen in on specific signals that are passing between one cell and another cell,” he explains.
Kotlikoff is also using the glowing heart cells to study stem cell transplants. “We can differentiate these [glowing] cells and put them into hearts that have been injured. The cells signal when they’re activated, so we can tell how they behave in their new environment.”
Igor Efimov, associate professor of biomedical engineering at Washington University in St. Louis, who studies the disruptions in electrical signalling that cause arrhythmias, says this work is a major breakthrough: “I think it will open a new opportunity for imaging, so that we can finally express intrinsic sensors in different compartments of the heart or brain and study how impulses are conducted under normal conditions, which is very important,” he says.
While Wier cautions that this research is still in its early stages, he says it is “promising compared to what we had in the past. This [work] is getting us closer to being able to see physiological changes, in the least invasive way.”