Optogenetics enables study of cardiac arrhythmias in nematodes

Optogenetics using a particular type of nematode could be used to to test substances for treating cardiac arrhythmias.

Oct 8th, 2015

Researchers at Goethe University (Frankfurt, Germany) used optogenetics to study the nematode Caenorhabditis elegans (C. elegans), a method that can be used to test substances for treating genetically mediated cardiac arrhythmias. They used the nematode feeding apparatus for this purpose, a rhythmically active muscle pump that resembles the muscle cells in the mammalian heart. This could be an important step towards personalized medicine.

Related: Optogenetics could work to correct life-threatening arrhythmias

Cardiac arrhythmias often have genetic causes. The same mutation is often detected in patients with the same type of arrhythmia. However, it is not clear from the outset whether other mutations in the same gene have the same effects. The effects of the arrhythmia could also differ depending on the type of mutation. This knowledge could definitely be significant for treatment because a type of medication that works particularly well for a specific mutation could be less beneficial for other mutations. Researchers have long been searching for a simple model that can be used to create certain genetic defects and in which the efficacy of substances can be tested.

The research group, led by Alexander Gottschalk at the Institute of Biochemistry and the Buchmann Institute at Goethe University, used C. elegans because it is easy to modify it genetically. The nematode feeding apparatus uses ion channels similar to those in muscle cells of the mammalian heart. Ion channels play an important role in regulating cardiac muscle excitation, and mutations in their genes often lead to arrhythmias.

The researchers used optogenetics since the feeding apparatus—the pharynx—does not naturally pump as regularly as required to recognize arrhythmias. They introduced photoactivated ion channels into the muscle cells using a genetic approach. In this way, the apparatus can be transformed into a light-activated muscle pump with highly regular action. They then introduced various ion channel mutations, which are responsible for the so-called Timothy syndrome (LQT8) in humans. In practice, the mutated pharynx then demonstrated aberrant pump behavior.

"We were able to improve or reverse these arrythmic effects using a substance that is already known to be pharmacologically active, and which is administered to patients with Timothy syndrome in a modified form," Gottschalk explains.

The goal is to use C. elegans to search for new active substances for other types of arrhythmia. These could even potentially be patient-specific if the exact mutation is transferred to the worm. The ease of genetic mutability of the nematode is highly advantageous in this regard when compared to a mouse model, which would be very difficult to generate.

Full details of the work appear in the journal Scientific Reports; for more information, please visit http://dx.doi.org/10.1038/srep14427.

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