Cav1.2 on Qube 384 – pharmacology, stability and CiPA

著者: Melanie Schupp, Rasmus Jacobsen, Mads P G Korsgaard

The voltage-sensitive L-type Ca2+-channel (LTCC) CaV1.2 is widely expressed in vascular smooth muscle tissue and the heart muscle1-3. The opening of the channels leads to an increase of intracellular calcium, which acts as second messenger and thereby affects a variety of cellular processes4 including heart muscle contraction and neurotransmitter release. CaV1.2 is therefore an important target in e.g. safety pharmacology screening. The 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 benzothiazepines5,6.
In this study, currents from CHO-hCaV1.2 were recorded on the high-throughput platform Qube 384 in multi-hole mode (10 patch holes per well) at both a customer’s site and at Sophion. Success rates, rundown, sealing properties and the pharmacological effects of two compounds were determined.