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hCaV1.2

hCaV1.2 assays on Chi­nese Ham­ster Ovary (CHO) cells

hCaV1.2 chan­nel plays an impor­tant role in the shape of the plateau phase and in the repo­lar­i­sa­tion of the car­diac action poten­tial. This chan­nel is also involved in the excitation-​contraction cou­pling mak­ing this chan­nel a key fac­tor in con­trac­tion of car­diac cells.
In the pre­clin­i­cal stage, 11% of com­pounds are stopped because of car­dio­vas­cu­lar effects and among these 11%, 73% of these car­dio­vas­cu­lar effects are related to con­trac­til­ity prob­lems.
A phar­ma­co­log­i­cal reduc­tion of the ICaL cur­rent may delay the repo­lar­i­sa­tion process and may lead to a pro­lon­ga­tion of the QT inter­val. Thus, CaV1.2 cal­cium chan­nel rep­re­sent a tar­get for the car­diac safety assessment.

Muta­tion LQT8

Stim­u­la­tion pro­to­col:
  • GLP com­pli­ant
  • stim­u­la­tion fre­quency: 0.1 Hz


Mea­sured para­me­ters:
  • Ampli­tude of the peak cur­rent upon depo­lar­iza­tion to 0 mV (pA)
  • Ampli­tude of the base cur­rent at –80mV (pA)
  • Inhi­bi­tion of CaV1.2 peak cur­rent amplitude (%)
  • IC50 value
Ref­er­ence com­pounds or pos­i­tive con­trols

REF­ER­ENCE

COM­POUNDS

IC50
ver­a­pamil 3.4 µM
nifedip­ine 2.8 nM
dil­ti­azem 7.7 µM

Tools:
The CaV1.2 cal­cium chan­nel avail­able at Phys­ioS­tim is expressed inCHO division-​arrested cells, sup­plied by ChanTest.