Light as a Silencer
Development of a New Optogenetic Tool to Study Complex Cellular Networks
Optogenetics permits specific manipulation of biological processes in single cells using light. Thereby behavior of single cells, cellular networks, organs and even whole organisms can be control with high time and spatial resolution. Optogenetics is very important for basic research because it made possible to study the function of specific cell types in an intact tissue. In addition, the new tool paves the way for the development of new treatments because for example it allows the study of missing electrical signals that take place after a heart infarct. Above all, scientists in neuroscience are planning new applications for investigation of neuronal networks.
Light-gated ion channels are proteins used to “switch-on” with light the activity of electrically excitable cells, and then study the regulation of electrical activity in complex cellular networks. Equally important is the use of optogenetic tools for “switch-off” or silencing of electrical activity. Indeed, the current established proteins are sufficient or have undesirable side effects.
Silencing of Excitable Cells
Dr. Yinth Andrea Bernal Sierra from the Humboldt-University of Berlin and Dr. Benjamin Rost from Charité together with colleagues from Berlin, Bonn, Freiburg and Martinsried have developed a new optogenetic tool for silencing of excitable cells. This two-component optogenetic tool is based on the simultaneous expression of a photoactivated enzyme (PAC) and a bacterial potassium channel (K). When PAC and K are together, a short pulse of blue light is enough to suppress the activity of heart cells and neurons for several seconds. In addition, through PACK activation movement in zebrafish can be arrested.
Besides its function as a silencer, one special feature of the new optogenetic system is a pronounced high light sensitivity. After activation of the PACK system by few photons (light quanta), the current flow through potassium channels drives the membrane potential to the natural resting membrane potential of the cell.
This type of silencing is energetic advantageous and diminishes undesirable side effects through unnatural ion fluxes that were inevitable with the current optogenetic inhibitory tools.
Yinth Andrea Bernal Sierra, Benjamin R. Rost, Martin Pofahl, António Miguel Fernandes, Ramona A. Kopton, Sylvain Moser, Dominik Holtkamp, Nicola Masala, Prateep Beed, John J. Tukker, Silvia Oldani, Wolfgang Bönigk, Peter Kohl, Herwig Baier, Franziska Schneider-Warme, Peter Hegemann, Heinz Beck, Reinhard Seifert, Dietmar Schmitz: Potassium channel-based optogenetic silencing, Nature Communications (2018); DOI: [10.1038/s41467-018-07038-8].