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SYNTHETIC STILBENE DERIVATIVE CONTROLS THE ACTIVITY OF VOLTAGE-GATED ION CHANNELS OF NEONATAL RAT CARDIOMYOCYTES

Name
Sheyda
Surname
Frolova
Scientific organization
Moscow Institute of Physics and Technology
Academic degree
Master
Position
Junior Researcher
Scientific discipline
Life Sciences & Medicine
Topic
SYNTHETIC STILBENE DERIVATIVE CONTROLS THE ACTIVITY OF VOLTAGE-GATED ION CHANNELS OF NEONATAL RAT CARDIOMYOCYTES
Abstract
The finding confirms that CTAB-effect on cardiac tissue excitability indeed results from modulation of voltage-gated ion channels responsible for the action potential generation. Thus, the effect of CTAB can be reversed by the washout and is completely irreversible after the UV irradiation. The latter fact gives the opportunity to permanently block the conduction in cardiomyocytes without destroying them.
Keywords
Synthetic Stilbene Derivative, Ion Channels, Patch Clamp, Photocontrol
Summary

SYNTHETIC STILBENE DERIVATIVE CONTROLS THE ACTIVITY OF VOLTAGE-GATED ION CHANNELS OF NEONATAL RAT CARDIOMYOCYTES

Sheyda R. Frolova*

1 Moscow Institute of Physics and Technology, Dolgoprudny, Russian Federation

A remote, easily reversible, and precise method for controlling excitable biological tissues, such as heart and neural networks, would have enormous potential for biomedical applications. The modulation of voltage-gated ion channels by azobenzene trimethylammonium bromide (azoTAB) and its influence on cardiac tissue excitability were recently reported. To reduce the toxicity of the photocontrolling substance, stilbene trimethylammonium bromide (CTAB) was synthesized. The structure of stilbene trimethylammonium bromide (CTAB) is very similar to the structure of azobenzene trimethylammonium bromide (azoTAB), with only difference that it is a derivative of stilbene. Presently, we have investigated that CTAB, just like azoTAB, is able to control the excitability of neonatal cardiomyocyte cell culture. Trans-CTAB blocks the excitation waves in cultured monolayers of cardiomyocytes. However, there is a significant difference between the action of cis-forms of azoTAB and CTAB. The blocking effect  of C-TAB remains after UV irradiation (λ~365 nm), when trans-CTAB turns to cis-CTAB, and stays permanently. The excitability of cardiac cell culture can be restored by washout of the cell monolayers from trans-CTAB.

As the membrane potential of cardiac cells is mainly controlled by the activity of voltage-gated ion channels, this study examined whether the sensitization effect of CTAB was exerted primarily via the modulation of the voltage-gated ion channel activity. For this purpose, we performed perforated whole-cell patch-clamp recordings from single ventricular cardiomyocytes, derived from neonatal rats under various conditions (with trans- and cis- isoforms of CTAB at visible and near-UV illumination, respectively).

The effects of trans- and cis- isomers of CTAB on voltage-dependent sodium (INav), calcium (ICav), and potassium (IKv) currents in isolated neonatal rat cardiomyocytes were investigated.  The experiments showed that CTAB modulated ion currents, causing suppression of the sodium (Na+) and calcium (Ca2+) currents and potentiation of the net potassium (K+) currents. We can restore the ion currents by washout cardiac cells from trans-CTAB. But after UV-irradiation (λ~365 nm) of the isolated cardiac cells  in the presence of CTAB the currents can not be restored. The modulation of the ion channels activity is occurred at a lower concentration of CTAB (60 μМ) than concentration of azoTAB (100 μМ). This finding confirms that CTAB-effect on cardiac tissue excitability indeed results from modulation of voltage-gated ion channels responsible for the action potential generation. Thus, the effect of CTAB can be reversed by the washout and is completely irreversible after the UV irradiation. The latter fact gives the opportunity to permanently block the conduction in cardiomyocytes without destroying them.