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.

Selected Publications

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

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., 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

Dempski, R.E., Friedrich, T.,Bamberg, E. (2005) The b subunit of the Na+/K+-ATPase follows
the conformational state of the holoenzyme.
Journal of General Physiology 125, 505-520).

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.

Zhang,F.,Wang,L.,Brauner,M,Liewald,J.Kay,K.,Watzke,N.,Wood,P.,Bamberg,E.,
Nagel,G.,Gottschalk,A., Deisseroth,K. (2007) Multimodal fast optical interrogation of neural circuits.
Nature 446,633-639.

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

Dempski,R.,Lustig,J.,Friedrich,T.Bamberg,E. (2008) Structural Arrangement and Conformational Dynamics of the Gamma Subunit of the Na+/K+ ATPase.
Biochemistry 47,257-266

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

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).