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

The voltage-sensitive L-type Ca²⁺-channel (LTCC) Ca_V1.2 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 acts as second messenger and thereby affects a variety of cellular processes⁴ including heart muscle contraction and neurotransmitter release. Ca_V1.2 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 benzothiazepines^5,6.
In this study, currents from CHO-hCa_V1.2 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.