Temperature effect on hERG channel pharmacology measured using the Qube automated patch clamp system
The human ether-à-go-go related gene (hERG) function is important for cardiac repolarization and inhibition of the channel can prolong the cardiac action potential, which gives increased risk for ventricular arrhythmias including torsade des points (TdP). Therefore, in vitro evaluations of the compound effects is performed on the hERG channel routinely in drug development projects to detect potential arrhythmic side-effects.
Usually these compound measurements are carried out at ambient temperatures. Previously it has been shown that the potency for many compounds has been underestimated when compared to near physiological temperature tests. Therefore, a temperature controlled measuring environment is beneficial when testing compounds for the aims as mentioned here.
Until recently, the only possibility to test compound potency under voltage control conditions has been the manual patch clamp technique. Now automated patch clamp instruments with temperature control have become available making it possible to perform up to 384 parallel recordings at controlled temperatures ranging from 8°C and above.
Here we used an automated patch clamp system, Qube, to study the effect of temperature on concentration response relationships on a panel of compounds known to block the hERG channel. Qube has a temperature controlled test environment and in these studies, we show that temperature merits being taken into consideration when evaluating for hERG pharmacology.