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Institut für Physiologie II - Herz-Kreislauf-Physiologie
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Physiology / Research fields / Sodium channels

Sodium channels

Development of novel optogenetic switches

The main aim of this project is to develop non-invasive tools for future application in basic science and medicine. Using genetically engineered fusion proteins consisting of subunits of voltage-gated sodium channels and of the light-sensitive cation channel Channelrhodopsin-2 (ChR2) we are able to elicit action potentials (APs) in normally unexcitable Xenopus oocytes and HEK293 cells by short blue-light flashes. This optogenetic method offers the possibility to prove basic questions regarding the effect of individual ion fluxes on the AP shape. Moreover, it allows us to study the AP-prolonging impact of naturally occurring ion channel mutations, associated with life-threatening arrhythmias, and the therapeutic potential of various antiarrhythmic drugs. Future research is aimed at transferring our novel optical switches to stems cells and cardiomyocytes.

Triggering of light-induced APs in Xenopus oocytes. The figure on the left shows the structure of one of our Nav/ChR2 fusion constructs (red – Nav channel, blue – ChR2 coupled as a dimer). The figure on the right shows three light-induced APs that were obtained after expression of the fusion construct alone (black line) and after co-expression of two delayed rectifier Kv channels (yellow line - Kv1.2, violet line - hERG). The blue bar represents the 30 ms light puls.
Triggering of light-induced APs in Xenopus oocytes. The figure on the left shows the structure of one of our Nav/ChR2 fusion constructs (red – Nav channel, blue – ChR2 coupled as a dimer). The figure on the right shows three light-induced APs that were obtained after expression of the fusion construct alone (black line) and after co-expression of two delayed rectifier Kv channels (yellow line - Kv1.2, violet line - hERG). The blue bar represents the 30 ms light puls.

Subject-related publications

vom Dahl, C., Müller, C.E., Berisha, X., Nagel, G., Zimmer, T. (2022)
Membranes  12, 907
Walther, F., Feind, D., vom Dahl, C., Müller, C.E., Kukaj, T., Sattler, C., Nagel, G., Gao, S., and Zimmer, T. (2020)

J. Gen. Physiol. 152, e201912489

Gütter, C., Benndorf, K., Zimmer, T. (2013)

Front Physiol. 4, 153

Walzik, S., Schroeter, A., Benndorf, K., Zimmer, T. (2011)
PLoS One 6, e19188

Contact

Prof. Dr. Thomas Zimmer

Phone: 03641 - 9 397655 / 9 397680