Ion Channel Screening Assays

Ion Channel Screening Assays

Aurora Biomed provides a wide range of ion channel assays to quickly and accurately provide results for drug discovery and development research worldwide. A convenient, integrated ordering system facilitates rapid assessment and processing of globally standardized tests. Assays are performed manually by patch clamp or by Qpatch. Cold flux assays are also available for limited compounds or candidates that cannot be screened with manual patch clamp, with a strong linear correlation (R=0.88) and consistently identical drug rank orders between the cold flux and patch clamp methods. Cold flux assays rely on non-radioactive trace ions measured by Aurora’s high-throughput atomic absorbance-based Ion Channel Reader series: ICR 8000 and ICR 12000.

Electrophysiological in vitro and in vivo studies required by the FDA are available on either stable cell lines, cells transiently expressing channels of interest, transformed Xenopus oocytes (two-electrode voltage clamp), cardiac myocytes (freshly isolated from rat or guinea pig), or neurons differentiated from human iPS. Please contact info@aurorabiomed.com for more information.

Frequently Asked Questions

Cells lines with stable or transient expression of the ion channels of interest are available for screening.  In addition, Aurora offers cardiac functional assays that include:

• Action potential recordings from isolated tissues (rabbit Purkinje fibers, atria, guinea pig papillary muscle, hiPSC-derived cardiomyocytes, isolated primary cardiomyocytes)

• Contractility assay (sarcomere shortening of isolated cardiomyocytes using the IonOptix system)

• Rabbit Torsades de Pointe model

• Left ventricular pressure-volume analysis on anesthetized animals

We recommend testing a minimum of 4 concentrations in triplicates for generation of a dose response curve and calculation of an IC50 value.

The hERG channel is an important contributor to cardiac repolarization. But, although Inhibition of hERG channels can lead to delayed repolarization, it does not necessarily lead to arrhythmia. The cardiac action potential results from the balance of activity of multiple ionic currents. Inhibition of hERG channels can have a limited impact when other ion channels are inhibited as well. Thus, it is important to assay the effects of test compounds on hERG (IKr), but also on Nav1.5 (peak and late sodium current), Cav1.2 (calcium current, ICa,L), KCNQ1/E1 (slow delayed rectifier, IKs), Kir2.1 (inward rectifier, IK1).

The ion channel of interest is usually expressed in mammalian cells such as HEK cells and its activity is recorded using the patch clamp method or high throughput systems (e.g. Aurora’s Ion Channel Reader). New cell systems (human iPSC-derived cardiomyocytes) are now available to assess effects of compounds on ion channels in a more physiologically relevant model. Action potential recordings from hiPSC-CM and rabbit Purkinje fibers are also valuable models to predict proarrhythmic liability. They complement the ion channel data.

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