Safety
 

One of the typical ion channels used in safety pharmacology is the hERG channel. A high percentage of hERG channel blockers are considered to be 'sticky' compounds, which often adhere to plastic surfaces. Due to the careful design of the NPC-1 chip, the test compounds only touch the glass surface during the experiment. Therefore the risk of losing compound is kept to a minimum.

The figures below show recordings from hERG channels expressed in CHO cells. Both figures display the typical IV-relationship.

 

 

One standard compound to block hERG channels is Terfenadine. Since it is known to bind to plastic surfaces, the solutions were prepared in glass containers. Four different concentrations of Terfenadine were applied to the same cell. The corresponding Hill fit is displayed on the right with a resulting IC50 = 22 ± 9 nM (n = 4).

 

Two more compounds were tested on HEK293 cells expressing the hERG channel.
The first compound is Cisapride and the corresponding Hill fit is displayed on the left. The resulting IC50 = 5.5 ± 1.9 nM (n = 6), corresponding well to values reported in the literature, which range from 5 – 60 nM. Five different concentrations were applied to the same cell.
The figure on the right shows the Hill fit of Flunarizine blocking hERG channels. The IC50 = 249 ± 57 nM (n = 4), in agreement with the value reported in the literature ( 344 nM).