High-throughput for cardiac ion screening strategies channels

In this article we discuss new technologies for high-throughput screening (HTS) of cardiac ion channels. We review the current state of-cell based HTS and discuss new technologies and approaches using voltage-sensing Fluorescence Resonance Energy Transfer (FRET) dyes and "native" cell lines. The advantages and disadvantages of a gene-centric approach in which a target protein is overexpressed in a non-native cell line are addressed and the role of such primary screens in the drug discovery process outlined. Primary and secondary screens using "native" type cell lines either endogenously expressing the ion channel of interest or overexpressing it are discussed with respect to HTS capacity and sensitivity for FRET voltage sensing dyes and other technologies. Finally the advantages and approaches of screening against multiple targets ill all endogenous cardiac cell line are discussed. (Trends Cardiovasc Med 200 1; 11:54-59). (C) 2001 Elsevier Science Inc.