Photoexcitation of the P4480 State Induces a Secondary Photocycle That Potentially Desensitizes Channelrhodopsin-2

• DOI: 10.1021/jacs.8b03931
• Publication Date: 2018-07-23T20:49:50Z
• Authors: Mattia Saita; Franziska Pranga-...; Tom Resler; Ramona Schlesinger; Joachim Heberle; Victor A. Lorenz-...
• Keywords: Photoexcitation; Intermediate state; Dark state; Channelrhodopsin

Channelrhodopsins (ChRs) are light-gated cation channels. In spite of their wide use to activate neurons with light, the photocurrents ChRs rapidly decay in intensity under both continuous illumination and fast trains light pulses, broadly referred as desensitization. This undesirable phenomenon has been explained by two interconnected photocycles, each them containing a nonconductive dark state (D1 D2) conductive (O1 O2). While D1 O1 states correspond dark-state P3520 intermediate primary all-trans photocycle ChR2, molecular identity D2 O2 remains unclear. We show that P4480, last photocycle, is photoactive. Its characterized time-resolved UV/vis spectroscopy, contains red-shifted intermediate, I3530. Our results indicate P4480 I3530 intermediates, connecting desensitization ChR2 photochemical properties intermediate.