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Researchers at Leipzig University and TU Dresden have succeeded in developing biological switches that can selectively turn ion channels on and off using light pulses. Initial applications show that it is possible, for example, to stimulate nerve cells in the brain or to control the release of adrenaline from cells of the adrenal gland and the movement of the small intestine using light stimuli. The research has now been published in the prestigious journal Nature Chemical Biology.
Ion channels act like selective gates in the dense cell membrane, as they regulate the targeted transport of ions such as sodium, potassium and calcium. Depending on the stimulus, these channels can open and close – for example in response to electrical signals, chemical molecules or intracellular messengers. They play important roles in many organs, including the brain, the adrenal gland and the digestive tract. At the heart of the current study are two ion channels from the so-called transient receptor potential or TRP family – TRPC4 and TRPC5. The key discovery is an efficacy switch: a new compound whose activity can be reversibly controlled by light, acting as a channel activator under violet light and as a channel inhibitor under blue light.
For this research, a team led by scientists from Leipzig University and TU Dresden combined compounds that influence the TRPC4 and TRPC5 channels with a chemical photoswitch, enabling the molecules to be switched “on” and “off”. The two novel molecules, named AzPico and AzHC, act as molecular photoswitches that enable channel activity to be controlled through targeted external light stimuli. What is distinctive about the study is that control is not limited to a simple on–off mechanism: instead, the intensity of the effect depends on the colour of the light used. The photoswitch therefore functions, quite literally, like a dimmer, allowing the effect to be finely regulated, with the chosen light colour corresponding to the control setting.
“With this new method, which we refer to as ‘chromocontrol’, it is possible to stimulate cellular or organ functions with very high spatial and temporal precision and with a precisely defined intensity,” explains Professor Michael Schaefer, Director of the Rudolf Boehm Institute of Pharmacology and Toxicology. The Leipzig University professor of pharmacology and toxicology led the study in collaboration with Professor Oliver Thorn-Seshold of TU Dresden. Initial applications include the activation of specific groups of neurons in the brain, light-regulated release of adrenaline from the adrenal gland, and light-controlled contraction or relaxation of the small intestine.
New photoswitches respond reliably
The precise binding sites of the two new photoswitches were elucidated through collaborations with Professor Robin Bon at the University of Leeds and Professor Stefan Raunser at the Max Planck Institute of Molecular Physiology in Dortmund, using high-resolution cryo-electron microscopy. In addition, experiments using genetically modified mouse lines showed that the TRPC4 and TRPC5 photoswitches act with a high degree of selectivity and specificity.
In follow-up studies, researchers are currently investigating additional organ systems in which the TRPC4 and TRPC5 ion channels play important roles. In parallel, successor compounds are being developed that can be activated using longer-wavelength light. This approach could enable reliable targeting of even deeper tissue layers. In the future, these new light-controlled molecules could help improve our understanding of complex physiological functions and support the development of new, regionally and temporally tunable therapeutic approaches.
Further information: The research was conducted within the DFG-funded Transregio Collaborative Research Centre 152. The project investigates biological functions and potential pharmacological targets within a group of ion channels known as transient receptor potential (TRP) channels. From the outset, the Leipzig research group has been part of this Collaborative Research Centre, serving as a screening hub with a particular focus on these channels.
Translation: Matthew Rockey
Professor Michael Schaefer
Leipzig University, Faculty of Medicine
Rudolf Boehm Institute of Pharmacology and Toxicology
Email: michael.schaefer@medizin.uni-leipzig.de
Original publication in Nature Chemical Biology:
“Ideal efficacy photoswitching for chromocontrol of TRPC4/5 channel functions in live tissues” DOI: 10.1038/s41589-025-02085-x https://www.nature.com/articles/s41589-025-02085-x
Professor Michael Schaefer
Quelle: Swen Reichhold
Copyright: Leipzig University
Shown is the spatial structure of the photoswitch bound within the TRPC4 channel – once in its inhib ...
Quelle: Michael Schaefer
Copyright: Leipzig University
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Biologie, Medizin
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Professor Michael Schaefer
Quelle: Swen Reichhold
Copyright: Leipzig University
Shown is the spatial structure of the photoswitch bound within the TRPC4 channel – once in its inhib ...
Quelle: Michael Schaefer
Copyright: Leipzig University
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