Pulses of light might one day keep diseased hearts beating

Saturday, November 13, 2010

LONDON - Heart muscles genetically engineered to respond to optical stimulation could improve models of heart attacks, and may also increase the understanding of how the embryonic heart develops, say scientists.

The works are among the earliest applications outside the nervous system of a technique called optogenetics. This approach switches cells on and off using proteins called channelrhodopsin and halorhodopsin, which are taken from microorganisms and act as light-sensitive ion channels.

When expressed in neurons, the proteins allow scientists to control individual neurons and brain circuits in laboratory animals using pulses of different colours of light.

Like neurons, heart-muscle cells - cardiomyocytes - are activated by electrical action potentials created by pumping ions into and out of the cells.

“If you had to pick the next logical tissue for work on optogenetics, the heart is a great one,” Nature quoted Karl Deisseroth, of the Stanford University, as saying.

Traditionally, physiologists use electrical currents to stimulate heart cells in culture or in living animals. But electricity produces toxic gases and alters the pH of the cells, preventing scientists from continuing the stimulation for very long, said Philipp Sasse, of the University of Bonn in Germany.

His team engineered embryonic stem cells from mice to contain the channelrhodopsin protein, which creates action potentials when bathed in blue light, then converted the cells into cardiomyocytes.

By briefly shining blue light onto one patch of cells, they made all the cells beat in unison. And when the researchers shone light onto cells that were already beating, those cells began to beat out of step with the rest - like a cardiac arrest in a petri dish, said Sasse.

The team used the same technique to produce transgenic mice whose cardiomyocytes responded to light. Shining blue light onto the hearts of these mice in different places made cells beat out of rhythm, simulating the arrhythmias that can stop hearts in humans, he said.

Another study, published in Science today2, saw researchers gain even greater control by engineering heart cells from zebrafish (Danio rerio) to contain both channelrhodopsin and halorhodopsin - which quiets beating cells when bathed with orange light.

The researchers then used a chip salvaged from an optical projector to control light and stimulate the heart cells of transparent zebrafish embryos between one and five days after fertilization.

“It is basically like showing a PowerPoint presentation to the fish,” said Jan Huisken, of the Max Planck Institute of Molecular Cell Biology and Genetics.

Early in their development, zebrafish embryos receive all the oxygen they need through diffusion rather than blood flow, so Huisken’s team could silence individual cardiomyocytes and cause temporary cardiac arrest without harming the fish.

They found that as the zebrafish aged, fewer and fewer ‘pacemaker’ cells in ever-smaller regions of the heart needed to be silenced to cause a cardiac arrest. (ANI)

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