Getting the blues makes the heart stumble

11 Oct 2010

Getting the blues has taken on a new meaning for a group of genetically modified mice at the University of Bonn.

 Scientists in the Institute of Physiology I at the University bred the mice to produce a type of light sensor called "channelrhodopsin" in the heart muscle. This also stimulates cardiac muscle to contract when triggered by blue light, enabling control of heart activity on demand, just by exposing it to blue light.

When stimulated with blue light the channelrhodopsin opens and positive ions flow into the cell. This causes a change in the cell membrane’s pressure, which stimulates cardiac muscle cells to contract.

"We have genetically modified mice to make them express channelrhodopsin in the heart muscle," explains Professor Dr. Bernd Fleischmann of the Institute for Physiology I. "That allowed us to change the electric potential of the mouse heart at will, enabling us to selectively produce conditions such as arrhythmia of the atrium or the ventricle."

These types of arrhythmia (or ventricular fibrillation) are among the most common causes of death after a heart attack. They develop when large quantities of cardiac cells die and are replaced with connective tissue. “This scar tissue has a different electrical activity than the healthy heart muscle and that makes the heart stumble,” said leader of the study, Professor Dr Philipp Sasse.

Normally, electric impulses spread across the heart from a natural pacemaker. This happens in a temporally and spatially tightly controlled manner, creating a closely coordinated contraction. However, if entire muscle areas decouple electrically, this mechanism no longer works: all of a sudden, certain parts of the heart pulse at their own rhythm. This causes the blood flow to come to a near-standstill.

The Bonn scientists can now trigger this decoupling through photostimulation. They can target just a few cells at a time or direct larger areas of the heart, allowing them to find out, for instance, which areas of the hollow muscle are especially sensitive to electric disruptions.

But why not simply stimulate the heart muscle with electrodes in order to make the heart lose its rhythm? “That can be done as well,” says Professor Sasse. “ But this method has unwanted side effects: if the electric stimulation lasts longer than a few milliseconds, toxic gases are produced, and the pH value changes.”

The consequences of a heart attack, which leads to permanent tissue damage, can of course only be studied in a very limited form when using short-term electric stimulation. Photostimulation is much more suitable: the cells will even withstand stimulations of several minutes at a time without problems.

Using channelrhodopsin in medical research is not fundamentally new, although so far it has mainly been used in neuroscience. For instance, scientists can use these light channels to direct the behavior of flies and mice - with nothing but blue light.

Reference

 Tobias Bruegmann Daniela Malan Michael Hesse Thomas Beiert Christopher J Fuegemann Bernd K Fleischmann & Philipp Sasse. Optogenetic control of heart muscle in vitro and in vivo. Nature Methods aop, (2010). doi:10.1038/nmeth.1512.