Ion Channel Assays

Especially for voltage-gated ion channels HTS technologies only recently became available. Initially, only radiometric binding or ion flux assays were used, but later fluorescent ion-chelating or membrane potential dyes such as DiBac4 were utilized for read-outs on FLIPR-like cellular imagers [77]. An alternative has been to use FRET-voltage sensor probes on readers capable of dual emission reading, such as VIPR™ and CellLux™ [78]. However, these dyes are prone to fluorescent assay artifacts and can only slowly follow changes in the membrane potential; thus, they do not provide the necessary temporal resolution of the signal. The reference technology for measuring ion currents across cellular membranes is patch-clamping, and automated systems such as the IonWorks® or IonWorks® Quattro (Molecular Devices) [79] have recently been introduced to the market.

These systems use premanufactured 384-well plates, in contrast to micropipettes in conventional electrophysiology, and can reach throughputs of up to 2500 data points per day [80]. In particular, for the measurement of the fast currents of voltage-gated channels, automated patch-clamp technologies will open new possibilities of directly addressing this target class in rapid screening with high fidelity [81].

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