Screening of Cardiac Ion Channels

Creative Bioarray focuses on advances in genomics and high-throughput drug screening to provide clients with screening services for cardiac ion channels. We provide high-quality ion channel screening, cardiac safety screening assays, and iPSC-derived cardiomyocyte screening services to facilitate the discovery of new cardiac drugs.

Introduction

Since cardiac action potentials reflect the activity of more than 20 ion channels, ion channel screening techniques are expected to accelerate cardiac drug discovery. A variety of drugs are currently available for the treatment of various heart diseases, and cardiac arrhythmias are an important part of the drug market. Drugs that can be used to treat arrhythmias act on a variety of ion channels, such as Na⁺, K⁺, and Ca²⁺ channels. All antiarrhythmic drugs act on ion channels directly or indirectly, thus confirming that ion channels are important drug targets. Although many current cardiac drugs are selective for cardiac targets, other equally useful drugs have complex modes of action against multiple targets. Addressing the complexities of cardiac disease states and assessing drug cytotoxicity is critical for drug discovery in cardiac disease.

Fig. 1 Representation of a cardiac ventricular myocyte with multiple ionic conductances. (Numann, 2001)

Cardiac Ion Channel Screening Services

Creative Bioarray focuses on new technologies for high-throughput screening (HTS) of cardiac ion channels, such as the use of cell-based patch clamps and new technologies using voltage-induced fluorescence resonance energy transfer (FRET) dyes and "native" cell lines to help clients test ion channels of interest, so as to screen compounds against these ion channel targets and test the ability of compounds to regulate the activity of ion channels. We provide our clients with:

• Automatic and manual patch clamp screening.
• Functional screening of ion channel targets in recombinant cell lines.

Cardiac Safety Screening Services

CiPA (comprehensive in vitro proarrhythmia assay) is a new recommendation for the cardiac safety assessment of preclinical drugs proposed by the US FDA, CSRC, HESI, and SPS. We use a variety of methods to help clients test the effects of compounds on a variety of ion channels, which is a necessary part of the cardiac safety evaluation of preclinical drugs.

• hERG detection service
• Na_v1.5 detection service
• Kir2.1 detection service
• K_v4.3 detection service
• KCNQ1/E1 detection service

iPSC-Derived Cardiomyocyte Screening Services

We have developed a series of high-quality assays to assess the effect of compounds on the electrophysiological properties of human iPSC-derived cardiomyocytes.

• Evaluation of the effects of compounds on the action potential recorded from iPSC-derived cardiomyocytes using the traditional manual patch clamp methods.
• Prediction of the risk of test compound-induced delayed ventricular repolarization and QT interval prolongation using multi-electrode array (MEA) assays.
• Monitoring of intracellular calcium transients of iPSC-derived cardiomyocytes in response to test compounds using FLIPR Penta assays.

As a part of the drug discovery program, electrophysiology experts at Creative Bioarray provide clients with high-quality cardiac ion channel screening services. Our client-focused flexibility and rapid delivery of high-quality data will accelerate your exploration of ion channels as potential new targets and your understanding of cardiovascular responsibility. If you are interested in our service, please contact us for more details.

Reference

1. Numann, R.; Negulescu, P. A. High-throughput screening strategies for cardiac ion channels. Trends in cardiovascular medicine, 2001, 11(2): 54-59.