Structural foundations of optogenetics: Determinants of channelrhodopsin ion selectivity

• DOI: 10.1073/pnas.1523341113
• Publication Date: 2015-12-24T01:07:30Z
• Authors: Andre Berndt; Soo Yeun Lee; Jonas Wietek; Charu Ramakrishnan; Elizabeth E. Stei...; Asim J. Rashid; Hoseok Kim; Sungmo Park; Adam Santoro; Paul W. Frankland; Shrivats M. Iyer; Sally Pak; Sofie Ährlund-Ric...; Scott L. Delp; Robert C. Malenka; Sheena A. Josselyn; Marie Carlén; Peter Hegemann; Karl Deisseroth
• Keywords: Channelrhodopsin; Chloride channel

Significance Channelrhodopsins are membrane proteins that enable cellular regulation of transmembrane ion conductance through light-gated pores; these have found application in optogenetics. This paper tests the hypothesis selectivity channelrhodopsins is determined by surface potential pore region: Cations conducted a negatively charged pore, and chloride ions has neutral positively residues. In confirming this applying resulting principles, we engineer improved chloride-conducting channels with higher conductivity. We also provide insights into distinct mechanisms underlying inhibition mediated higher-efficiency compared pumps. Finally, demonstrate initial utility microbial opsin-based controlling behavior freely moving animals.