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Abstract

hERG (human ether-à-go-go-related gene) encodes a potassium ion channel which involved in ventricular repolarization at the end of a cardiac action potential. Mutations in hERG channel result in torsade"s de pointes. The cardiotoxicity is mainly due to the prolongation of the QT interval caused by the blockage of hERG. Indeed, many therapeutic drugs are withdrawn from the market as well as drug candidates may fail in the late phases of drug discovery because of cardiotoxicity. The ICH S7B and ICH E14 are the safety pharmacology guidelines recommended for evaluating new chemical entities. In the early phase of drug discovery, it is important to screen the compound for the activity on the hERG channels. Many hERG assays are available, including Fluorescent Membrane Potential Sensitive Dye Method, Radioactive Ligand Binding Method, Fluorescence Polarization Ligand Binding Method and Rubidium Flux method, Manual Patch-Clamp Method and automated Patch-Clamp Method, Langendorff"s perfused isolated heart method, Non-Invasive Telemetry, and Wireless Telemetry. This review is focused on hERG assay and provides additional information about the long QT syndrome and molecular structure of hERG. INTRODUCTION:The action potential is considered an electrical basis for the heartbeats, which starts from the specialized pacemaker cells and is transmitted to the atrial, ventricular muscles, and cardiac myocytes. Action potential involves the movement of ions into and out of cardiac myocytes through voltage-gated channels. It includes different phases Fig. 1. Phase 1 -Inactivation of Na + channels followed by K + channels that rapidly open & close, causing a transient outward current.