Development of a Cav 1.3 channel assay using optogenetic methods

Cav1.3 is a L-type voltage-gated calcium channel and an important therapeutic target for drug discovery. It has been shown that a number of drugs exhibit state dependent effects on Cav1.3 channels, meaning the potency of these drugs vary in response to the membrane voltage (Vm) and the consequent change of channel states (open, close, inactivated). As this likely provides highly-desired selectivity for pathologically over-activated Cav1.3 channels, there is a growing demand for the development of high-throughput assays to evaluate channel blockers under different states.

Current screening methodologies for this channel utilize either electrophysiology or fluorometric methods using potassium challenge to modulate membrane potential, yet both approaches have significant limitations.

In this study, we demonstrate the novel utility of optogenetic tools to control Vm in a reversible and precise fashion for screening state-dependent calcium channel blockers using the FLIPR System.

Development of a Cav 1.3 channel assay using optogenetic methods on the FLIPR Tetra System