Non-desensitizing Channelrhodopsin

12 03 2009

One of the problems with Channelrhodopsin-2 is that it desensitizes during continuous illumination or at high illumination frequencies. This limits the application of ChR2 to systems where high spike rates are not used to code information.

Desensitization of various Channelrhodopsins

Desensitization of various Channelrhodopsins

In Characterization of Engineered Channelrhodopsin Variants with Improved Properties and Kinetics, John Lin reports a new Channelrhodopsin, ChIEF, that has increased single channel conductance, faster kinetics and much less desensitization. This allows much higher rates of action potential generation. The in vitro results look great!

Success of action potential firing for ChR2 and ChIEF for various frequencies

Success of action potential firing for ChR2 and ChIEF for various frequencies

However, ChR2 has a relatively small effective expression window.  Too little expression and you cannot drive spiking.  Too high and the cell gets sick.  Tuning this expression is finicky. For ChIEF, it remains to be seen how the lack of desensitization, which might cause additional current leak in the resting state, effects this expression window in vivo. It certainly looks like its worth testing in your system of choice.



One response

13 03 2009

is it known why ChR2 makes cells sick?
In contrast, very high expression of YFP does not seem to do this.
Gordon Shepherd has a nice paper showing some small problems with H-line mice. (Front. Neural Circuits (2008) 2:6-doi 10.3389/neuro.04.006.2008)
My feeling is there is a very high level of YFP in these neurons.

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