L-type Calcium Channel Drug Testing

Millipore Corp. has added the human L-type calcium channel, a voltage-gated channel involved in normal myocardial and vascular smooth muscle contractility, to its CardiacProfiler Service for compound liability testing. A link between hERG channel block, QT prolongation and the ventricular tachyarrhythmia Torsades de Pointes (TdP) has been established, revealing the need to assess the cardiac risk of potential drugs. Recombinant cell lines that express multiple subunit ion channels are an integral part of testing novel compounds, yet developing these cell lines is complicated. Millipore’s PrecisION hCav1.2 recombinant cell line stably expresses three subunits and has been developed and validated to meet biophysical and pharmacological properties of the L-type calcium channel found in the human heart. For the L-type calcium channel, the precise timing of opening, inactivation and closing the channel mirrors the coordinated beating of the heart. Non-cardiovascular drugs should avoid an L-type blocking action at clinically relevant concentrations because such activity may cause cardiac side-effects. In some cardiovascular drugs with significant hERG block, L-type calcium channel blocking may be beneficial because the mixed-channel block action may not prolong the QT interval, thereby making it a safe drug. The CardiacProfiler Service offers compound profiling against the L-type calcium channel assessed either as a stand alone service or as part of a panel of other cardiac ion channels, including hERG, Nav1.5, KCNQ1/minK, Kv1.5, Kv4.3/KChIP1 and HCN4.