Ion channel over expressing cell lines for inhibitory screening

TRPV1 ion channel. Brauchi S et al. (2007).

In a recent post on  Venomous toxin ion channel modulators, we looked at toxin derived peptides to manipulate a wide variety of ion channels. These toxins can be used as tools to characterize specific ion channels, but they can also be utilized as reference inhibitors in ion channel drug screening campaigns.

Today, let’s take a look at cell lines over expressing specific ion channels and designed for cell based ion channel assays in drug discovery.

Ion channels are proteins with pore-forming abilities. Their selective capabilities to let ions cross the cell membrane involves them in crucial cellular functions (controlling membrane potential, the flow of ions, regulating cell volume). As ion channels are involved in the patho-physiology of so many diseases, they are natural candidates for pharma R&D programs.

To screen for ion channel inhibitors, cell lines are needed to expose functional ion channels to potential drug candidates. These cells lines have to stably express the ion channel of interest and should be characterized in terms of functionality of the respective channel.

Ion channel over expressing cell lines

BPS Biosciences have developed a set of cell lines with interesting targets for drug discovery campaigns. Most of these cell lines have been characterized with influx experiments.

They cover diverse ion channels classes, such as Calcium-, Potassium-, and Sodium-channels and others.

Ion channel over expressing cell lines for inhibitory screening - A practical example with TRPC3 cell line

TRPC3 produced constitutive Ca2+ entry in the presence of 5μM Gd3+ when expressed in HEK293. A) WT-HEK293 cells; B) TRPC3-HEK293 cells. Cells were incubated in the absence of added Ca2+, and 2mM Ca2+ was added where indicated. To block endogenous store depletion-induced Ca2+ entry, 5 μM Gd3+ was present throughout. The calcium measurements were performed using calcium indicator, Fluo-8 (excited at 485/20nm and emission at 528/20 nm).

Ion channel over expressing cell lines for inhibitory screening - A practical example with TRPC3 cell line - ERG cell line

Thallium influx in hERG-HEK293 cells is blocked by cisapride or dofetilide. (A) hERG-HEK293 or (B) parental HEK293 cells were loaded with the thallium-sensitive fluorescent dye Thallos (TEFLABS) and treated with DMSO (black), 1 μM of cisapride (pink), or 1 μM of dofetilide (green). Cells were then stimulated (60s) with stimulus buffer containing thallium and potassium. The thallium influx, as a surrogate indicator of hERG channel activity, .was measured by Thallos fluoresecence (excitation 490 nm and emission 515 nm)

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Written by Ali El Baya, PhD
Ali el Bayâ is the Sales Manager at tebu-bio for the North of Europe.