IC50 of compound for hERG

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zhangxu04
zhangxu04's picture
IC50 of compound for hERG

to determine the IC50 of compound for hERG is very important
but I am nor sure how to perform this.
A company tell that I can perfuse the cell with different concentration with out washing. in other words,  first to perfuse a low concentration drug, and then a higher concentation  and then a even higher concentration...
but I am afriad this will cause the  accumulating effect
soem tell me perfuse the cell with different concentration with out washing in other words,  first to perfuse a low concentration drug, and then washing out and then a higher concentation ,and washing out  and then a even higher ...
but I am afraid this need a long time (more than ) so it will be not suitable
 
and aslo it is suggested I can measure the current with one concentration for one cell
I want to know which is best for drug screening 

The FFM
The FFM's picture
As long as you establish good

As long as you establish good baseline conditions (i.e. establish a run-down compensation protocol) either technique will work.  If you are patching only 1 cell per dose, the I would hope the run down would not be an issue but for serial applications of drugs look for suitablke run doem compensation techniques.  there a re papers and discussions elsewhere on this site if you search for hERG and Rundown.
However it is fine to sequentially apply hERG blocking compounds because for the majority of them the wash out is so slow and often incomplete that washing out is not appropriate in a hERG dose response experiment.
 

zhangxu04
zhangxu04's picture
thank you very much.

thank you very much.
you mean sequentially apply the compounds with increasing concentration will be ok. but I worried that there will be a the  accumulating effect . for one example a low concentration of drug will block 10% of the current , and then (30 second) I give the same drug at higher concentration, blocking 50% . I ant to know if I can say the the high concentration drug can block 50% ? 
I think this will be a great issue. 
 
plase gvie your opinion . 

Fraser Moss
Fraser Moss's picture
If you are really worried

If you are really worried about that perform the control experiment for one of the drugs where you sequentially apply the drugs and then repeat it when you do only one dose per cell.
Then compare the curves to see what the error is.