The main interest is to understand structure/function relationships of membrane proteins, preferably ion channels, by the use of molecular biological, electrophysiological optical and mathematical approaches. Thereby, we focus on cyclic-nucleotide dependent CNG and HCN channels, voltage-gated sodium channels, as well as ionotropic P2X and metabotropic glutamate receptors. The scientific cooperation within the CRC/TRR 166 “ReceptorLight” as well as within the Research Unit 2518 “DynIon” was intensified. Since July 2020, DynIon has been successfully continued in the 2^nd funding period. Together with the Institute of Physiology I, we are teaching physiology in lectures, seminars and practical courses.

Prof. Dr. Klaus Benndorf
Nonnenplan 9
07743 Jena

Institute of Physiology 2 - Cardiovascular Physiology

Research projects

Scrutinizing the function of the cyclic-nucleotide binding domain in the activation of HCN channels

Principal investigators: Dr. Jana Kusch, Prof. Dr. Klaus Benndorf
DFG 2017-2023

In project P2, we study the function of the C-linker and the cyclic nucleotide binding domain (CNBD) in mammalian HCN (hyperpolarization-activated and cyclic nucleotide modulated) channels. Confocal patch-clamp fluorometry (cPCF), a technique that combines electrophysiological approaches and confocal fluorescence microscopy will be applied. The data are interpreted kinetically by MD simulations in collaboration with Holger Gohlke (University Düsseldorf).

Homepage DFG Research Unit DynIon

Kinetic characterization of metabotropic glutamate receptors

Principal investigator: Prof. Dr. Klaus Benndorf
DFG (SFB/TR 166) 2015-2020

Metabotropic glutamate receptors (mGluRs) are G-protein coupled receptors, forming obligatory dimers. We investigated the glutamate-induced kinetics of the receptors using FRET in membrane patches exposed to fast concentration jumps. We were able to resolve the kinetics of mGluR1, proving a speed comparable to Rhodopsin. The study was extended to all 8 known mGluR isoforms, while also investigating their potential heteromeric forms and their kinetics.

Novel approaches to study the signal chain of the voltage-dependent gating in the selectivity filter of viral K+ channels

Principal investigator: Prof. Dr. Indra Schröder

DFG (FOR DynIon) 2020-2023

The selectivity filter of potassium channels has a dual function, recognizing ion species and simultaneously acting as a physiological gate. Using minimal viral model potassium channels (Kcv), we investigate how the ions within the selectivity filter and different mutations modulate this gate with a combination of experiments in artificial membranes and model-based analyses that take structural data into account. The project is part of the DFG research group 2518 'DynIon'.

The role of voltage-gated ion channels for cardiac excitation

Principal investigator: apl. Prof. Dr. Thomas Zimmer

The aim of our project is to better understand excitation processes in the normal and diseased heart by electrophysiological and molecular biology techniques. This includes optogenetic investigations on the effect of individual ion channels on action potentials, the identification of genotype-phenotype correlations in cardiac channelopathies, investigations on the therapeutic effect of antiarrhythmic drugs, and the development of novel optogenetic tools.

Selective modulation of rod and cone CNG channels using novel cGMP analogues: Perspectives for the treatment of retinitis pigmentosa

Principal investigator: Dr. Vasilica Nache
DFG 2020 - 2023

Retinitis pigmentosa is the most common form of inherited retinal degeneration and is characterized by progressive vision loss that eventually leads to complete blindness. Currently, there is no drug therapy available. The aim of this project is to develop and functionally characterize selective modulators of retinal cyclic nucleotide-gated channels (CNG). In addition, the therapeutic potential of these compounds in retinal-degenerative diseases characterized by a disruption of cellular cGMP homeostasis will be investigated.

Further projects

Direct visualizing of the binding cooperativity of HCN receptors

Principal investigators: Dr. Ralf Schmauder, Prof. Dr. Klaus Benndorf

since 2020
Bayesian analysis of ion channel kinetics for patch-clamp and confocal patch-clamp fluorometry data

Principal investigators: Dr. Ralf Schmauder, Prof. Dr. Klaus Benndorf

since 2020

Selected publications

Sattler, C., Eick, T., Hummert, S., Schulz, E., Schmauder, R., Schweinitz, A., Unzeitig, C., Schwede, F., and Benndorf, K. (2020) Unravelling the intricate cooperativity of subunit gating in P2X2 ion channels Sci. Rep. 10, 21751
Walther, F., Feind, D., vom Dahl, C., Müller, C.E., Kukaj, T., Sattler, C., Nagel, G., Gao, S., and Zimmer, T. (2020) Action potentials in Xenopus oocytes triggered by blue light J. Gen. Physiol. 152, e201912489
Sattler, C., Schmauder, R., Schwabe, T., Schweinitz, A., Unzeitig, C., Schwede, F., Otte, M., and Benndorf, K. (2020) Relating ligand binding to activation gating in P2X2 receptors using a novel fluorescent ATP derivative J. Neurochem. 154, 251-262
Leypold, T., Bonus, M., Spiegelhalter, F., Schwede, f., Schwabe, T., Gohlke, H., and Kusch, J. (2019) N6-modified cAMP derivatives that activate protein kinase A also act as full agonists of murine HCN2 channels. J. Biol. Chem. 294, 17978-17987
Grushevskyi, E. O., Kukaj, T., Schmauder, R., Bock, A., Zabel, U., Schwabe, T., Benndorf, K., and Lohse, M. J. (2019) Stepwise activation of a class C GPCR begins with millisecond dimer rearrangement Proc. Natl. Acad. Sci. U S A 116, 10150-10155

Outstanding achievements

In 2019, the institute hosted the International Symposium of the CRC TransRegio 166 - ReceptorLight.

PD Dr. Indra Schröder successfully applied for funding from the DFG's Heisenberg program in 2020. She was appointed to a Heisenberg professorship in 2021.