CaV1.2 - "High Throughput Pharmacology of CaV1.2 Channels on Nanion’s SyncroPatch 384PE"
SyncroPatch 384PE application note: (2.7 MB)
Cells were kindly provided by SB Drug Discovery.
The CaV1.2 channel is a voltage-gated calcium channel (VGCC) expressed in a variety of mammalian tissues and is essential for multiple processes including CNS function, cardiac and smooth muscle contraction and neuroendocrine regulation. VGCC are composed of 4 subunits, which include an alpha 1 subunit which forms the Ca2+-selective pore, contains the voltage sensor and many of the binding sites for regulatory modulators and drugs and accessory subunits α2δ, β and γ which are involved in anchorage, trafficking and regulatory functions. The CaV1.2 channel contains the alpha-1C subunit, encoded by the CACNA1C gene on the human chromosome 12p13. Mutations in the L-type Ca2+ channels have been associated with inherited arrhythmic disorders such as Timothy, Brugada and early repolarization syndromes. In addition, in the light of the CiPA initiative, the L-type channel is likely to become an important target for cardiac safety testing. Here we present high quality data with reliable pharmacology on CaV1.2 expressing HEK cells at a high throughput collected on the SyncroPatch 384PE. Current-voltage plots and concentration response curves for the compounds nifedipine and verapamil are shown. The IC50 values for these compounds are within the expected range and success rates of >75% for completed experiments were recorded. Importantly, CaV1.2 recorded on the SyncroPatch 384PE exhibited stable peak amplitude during the course of the experiment and displayed little or no rundown.