UV radiation can control cardiomyocyte function – with intriguing therapeutic possibilities
William Aryitey |
The ability to easily and reversibly control excitable biological tissue has potential for many biomedical applications. Now, researchers from the Moscow Institute of Physics and Technology (MIPT) have found a way to turn cell function on and off at the flick of a switch. They’re using azobenzene trimethylammonium bromide (azoTAB) and UV radiation to control voltage-gated ion channels in cultured rat cardiomyocytes (1).
“Initially, we were studying the behavior of excitation waves in heart tissue models, which can induce lethal arrhythmia,” says Konstantin Agladze, lead researcher and Head of the MIPT Biophysics of Excitable Systems Laboratory. Having identified the cells responsible for the excitation waves, the team set out to find a way to control them. Their research led to azoTAB, a compound based on azobenzene - which can be used as a 'photo-switch' when two of its rings are connected.
UV radiation changes the shape – and consequently the activity – of azoTAB. In visible light azoTAB potentiates the K+ current, while suppressing Na+ and Ca2+ currents, which blocks contractions. When exposed to UV light, azoTAB changes form, resulting in normal function of K+, Na+ and Ca2+ currents, so that the cell can once again contract. “We also have some preliminary data showing that azoTAB makes photocontrol of neural cells possible,” adds Agladze.
The researchers have been putting the photo-switch to good use by controlling cardiomyocyte rhythm across a sheet of cells in vitro, which could pave the way to potential treatments. The idea of turning off dangerous arrhythmia simply by applying light is certainly appealing. However, it’s likely to be many years before the technology is seen in the clinic – for one thing, azoTAB is too toxic for use in a living heart. To that end, the researchers are working towards developing far less toxic chemical substances but with photo-sensitive properties akin to azoTAB. “Our next step is to use these non-toxic analogs to experiment on whole animal hearts,” says Agladze.
- SR Frolova et al., “Photocontrol of voltage-gated ion channel activity by azobenzene trimethylammonuium bromide in neonatal rat cardiomyocytes”, PLoS One, 11 (2016). PMID: 27015602.