Researchers can genetically engineer mouse and zebrafish heart muscles to respond to light, according to two recently published studies. To carry out these studies, the research teams applied the technique of optogenetics, which uses proteins called channelrhodopsin and halorhodopsin. These proteins, which are taken from microorganisms, are light-activated ion channels. By expressing these proteins in neurons, scientists have previously used light to control the activity of individual neurons and of brain circuits in animals.

Both neurons and heart muscle cells are activated by electrical action potentials. An influx of ions into activated voltage-gated ion channels that lie in the plasma membranes of these cells generates these action potentials. To electrically stimulate heart muscle cells in the lab, scientists typically apply an external electric field to locally induce action potentials. But this approach produces toxic gases and can only be used for short durations, thereby limiting its utility.

Credit: Maxim Borovkov

To try to overcome such limitations, Philipp Sasse and colleagues from the University of Bonn in Germany decided to use the channelrhodopsin protein (Nat. Methods 7, 897–900; 2010). They generated a transgenic mouse stem cell line that expressed channelrhodopsin, which produces action potentials when exposed to blue light. The team then converted these channelrhodopsin-expressing stem cells into heart muscle cells. They exposed a group of these cells to blue light, which caused the cells to start beating in unison. Shining blue light on a sub-group of heart cells that were already beating caused the sub-group to start beating out of sync.

Sasse and colleagues then generated transgenic mice from the channelrhodopsin-expressing embryonic stem cells. To analyze the effect of channelrhodopsin activation in vivo, the researchers intubated and ventilated the channelrhodopsin-expressing mice, used a microscope to shine blue light onto the beating hearts of these mice and recorded electrocardiogram measurements from these mice. They were able to use light pulses as short as 1 millisecond to stimulate the hearts of these mice.

Another research group generated transgenic zebrafish that expressed both channelrhodopsin and halorhodopsin (which, when exposed to orange light, silences beating heart cells). Didier Stainier of the University of California, San Francisco and colleagues were able to use optical tools to find 'pacemaker' cells and to simulate tachycardia, bradycardia, atrioventricular blocks and cardiac arrest in these zebrafish (Science 330, 971–974; 2010). These optogenetic techniques could be used to improve understanding of embryonic heart development and to develop better heart attacks models.