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
"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.
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.