Light-gated ion channels. Recently, a novel class of ion channels, the light-gated channelrhodopsins (ChR1 and ChR2) has been discovered. They possess a seven transmembrane helix motif similar to that of other microbial rhodopsins and were investigated in part by electrophysiological methods in heterologously expressing cells (Nagel et al, 2002, 2003, 2005b). These channels represent a long sought-after and unique tool for neurobiological applications (Fig. 1) because they allow the light-induced depolarization of cells. This was demonstrated in nerve cells as well as in excitable cells in transgenic animals by induction of light dependent behavior as well as restoration of light reactions in a blind mouse. Meanwhile, ChR2 has found a worldwide application in many neurobiologically oriented laboratories. The mechanism of these ion channels is still unknown. Therefore, the function and structure of these membrane proteins need to be investigated in detail. By determining simultaneously the photocycle and the kinetics of the channel current the spectroscopic intermediate of the photocycle, which represents the open state of the channel, was identified (Bamann et al, 2008). By noise analysis the single channel conductance was determined to 35 fS. In the same paper it was demonstrated that ChR2 acts as a leaky light-driven proton pump (Feldbauer et al, 2009). In the future we are searching to construct channelrhodopsins with higher light sensitivity and larger single channel conductance, which would be desirable for neurobiological applications. New molecules are under construction which allow the activation and inactivation of nerve cells at different wavelengths with high spatial precision.
Structural analysis by 2D and 3D crystallization is under study with the Departments of Structural Biology and Molecular Membrane Biology.
The group is a member of an international consortium on the recovery of vision by use of ChR2 and of the Bernstein Center for Computational Neuroscience Göttingen for network analysis.
Fig. 1a: Light-activated action potentials in neuronal cells expressing ChR2. Three different hippocampal neurons (V~-65 mV). Deliveries of the same temporally patterned light stimulus using 10 ms duration light pulses (Boyden et al, 2005).
Fig 1b: Schematic representation of the light activation of ChR2
Kleinlogel, S., Terpitz, U., Legrum, B., Gükbuget, D., Boyden, E.S., Bamann, C., Wood, P.G. and Bamberg, E.: A gene-fusion strategy for stoichiometric and co-localized expression of light-gated membrane proteins. Nat. Methods 8, 1083-1088. (2011).
Kleinlogel, S., Feldbauer, K., Dempski, R., Fotis, H., Wood, P., Bamann, C., and Bamberg, E.: Ultra light-sensitive and fast neuronal activation with the Ca(2+)-permeable channelrhodopsin CatCh. Nat Neurosci 13, 13 (2011).
Yonehara, K., Balint, K., Noda, M., Nagel, G., Bamberg, E. and Roska, B.: Spatially asymmetric reorganization of inhibition establishes a motion-sensitive circuit. Nature 469, 407-410 (2011).
Bamann, C., Gueta, R., Kleinlogel, S., Nagel, G. and Bamberg, E.: Structural Guidance of the Photocycle of Channelrhodopsin-2 by an Interhelical Hydrogen Bond. Biochemistry 49 (2), 267-278 (2010).
Bamann, C., Nagel, G. and Bamberg, E.: Microbial rhodopsins in the spotlight. Curr. Opin. Neurobiol. 20, 610-616 (2010).
Hofmann, B., Maybeck, V., Eick, S., Meffert, S., Ingebrandt, S., Wood, P., Bamberg E. and Offenhäusser, A.: Light induced stimulation and delay of cardiac activity. Lap Chip 10, 2588-2596 (2010).
Verhoefen, M.-K., Bamann, C., Blöcher, R., Förster, U., Bamberg, E. and Wachtveitl, J: The Photocycle of Channelrhodopsin-2: Ultrafast Reaction Dynamics and Subsequent Reaction Steps. ChemPhysChem 11, 3113-3122 (2010).
Feldbauer, K., Zimmermann, D., Pintschovius, V., Spitz, J., Bamann, C., Bamberg, E.: Channelrhodopsin-2 is a leaky proton pump. Proc. Natl. Acad. Sci. 106 12317-12322 (2009).
Bamann,C., Kirsch,T., Nagel,G.Bamberg,E. (2008) Spectral characteristics of the photocycle of channelrhodopsin-2 and its implication for channel function.
J. Mol. Biol. 375,686-694
Kalmbach,R., Chizhov,I.,Schumacher,M.,Friedrich,T.,Bamberg,E. Engelhard,M. (2007) Functional Cell-free Synthesis of a Seven Helix Membrane Protein: In situ Insertion of Bacteriorhodopsin into Liposomes.
J. Mol. Biol 371,639-648
Nagel,G.,Gottschalk,A., Deisseroth,K. (2007) Multimodal fast optical interrogation of neural circuits.
Boyden, E.S., Zhang,F., Bamberg,E., Nagel,G., Deisseroth,K. (2005) Millisecond-timescale, genetically targeted optical control of neural activity.
Nature Neuroscience 8(9):1263-1268.
Nagel, G., Szellas, T., Huhn, W., Kateriya, S., Adeishvili, N., Berthold, P., Ollig, D., Hegemann, P., Bamberg, E. (2003). Channelrhodopsin-2, a directly Light-gated Cation-selective Membrane Channel.
Proc. Natl. Acad. Sci. 100, 13940-13945
Geibel, S., Kaplan, J.H., Bamberg, E., Friedrich, T. (2003).Conformational Dynamics of the Na+/K+-ATPase probed by voltage clamp fluorometry.
Proc. Natl. Acad. Sci. 100, 964-969
Nagel, G., Ollig, D., Fuhrmann, M., Kateriya, S., Musti, A.-M., Bamberg, E., Hegemann, P. (2002) Channelrhodopsin-1, A Light-Gated Proton Channel in Green Algae.
Science 296, 2395-2398
Prof. Dr. Ernst Bamberg, Director
Department of Biophysical Chemistry
Secretary: Heidi Bergemann
Phone: +49 (0) 69 6303-2000/2001
Fax: +49 (0) 69 6303-2002
Postdocs and staff scientists:
Ph. D. Students: