We are happy to invite you to our European Sophion User Meeting on 7th and 8th September and we are very pleased to announce that Sanofi in Paris kindly has offered to host the meeting this year.
We are preparing an interesting programme starting at noon on 7th September giving everyone a chance to travel to Paris in the morning. Wrap-up on 8th September just around lunchtime.
À bientôt
Sponsors:
Hope to see you at the annual Safety Pharmacology Meeting 2017 in Berlin. Meet us at booth #113 and speak with our ion channel experts on site.
When: 24th to 27th September
Venue: Maritim Hotel Berlin
Poster presentation (Poster #022)
Temperature effect on hERG channel pharmacology measured by using the Qube automated patch clamp system.
Abstract:
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 give 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 have 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 come available making it possible to perform up to 384 parallel recordings at controlled temperatures ranging from 18°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 potency.
We are working with the final details for this years’ agenda and we are very proud of the line up. Again this year we have a good programme with excellent speakers and interesting topics.
You can see the agenda here.
For a long time, screening assays on CaV1.2 have been challenged by the tendency of CaV1.2 cell lines to exhibit declining current levels in the course of the experiment. Here we report a robust assay with high success rates and reliable pharmacology.
The voltage-sensitive L-type Ca2+-channel (LTCC) CaV1.2 is a crucial component for controlling intracellular activity and thereby essential in the cardiovascular and neuronal system. It is widely expressed in vascular smooth muscle tissue and the heart muscle 1-3. The opening of the channels leads to an increase of intracellular calcium, which act as second messenger, and thereby affects a variety of cellular processes 4 including heart muscle contraction and CaV1.2 is therefore an important target in e.g. safety pharmacology screening. CaV1.2 channels are known to require a large depolarization for their activation and once activated they display a long-lasting current flow, which typically can be blocked by low micromolar concentrations of e.g. dihydropyridines, phenylalkylamines and benzothiazepines 5,6.
In these studies, currents from HEK-hCaV1.2 were recorded on the high-throughput platform Qube 384 in both single-hole and multi-hole mode. Success rates, IV characteristics and the pharmacological effects of three different compounds were determined.