New versions of channelrhodpsin 2, ReaChR and VChR1 with improved kinetics and light-sensitivity

ChR2 can be employed for light-induced depolarization, however, there is an ongoing investigation on ChR2 mutants with faster kinetics and increased light-sensitivity for potential clinical applications.

Scientists from the Max-Planck-Institute of Biophysics in Frankfurt constructed faster ChR2 mutants based on the modification at position F219 in helix 6 of the seven transmembrane helix motif. This mutation in wildtype ChR2 accelerates the closing time (off-kinetics) of the channel. Interestingly, in CatCh the modification in helix 6 display a 20-fold increase of Ca²⁺ permeability. The newly discovered effect was verified in ChR2, VChR1 and in the chimera ReaChR. Of note, the considered positions are homologous among different ChRs in helix 6.

The use of these new variants will provide a light stimulation of neurons up to 800 to 1000 Hz. Further, the modification leads to an increase in Ca²⁺ permeability as a tool to influence the Ca²⁺ concentration in the cytosol.

In general, this finding contributes to the development of high-throughput screening platforms and can be applied for stimulating neurons.

A priority application was filed in June 2016 (WO2017207745). Nationalization in EP, CN, US, KR and JP.

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