title: Novel screening techniques for ion channel targeting drugs.
abstract: Ion channels are integral membrane proteins that regulate the flux of ions across the cell membrane. They are involved in nearly all physiological processes, and malfunction of ion channels has been linked to many diseases. Until recently, high-throughput screening of ion channels was limited to indirect, e.g. fluorescence-based, readout technologies. In the past years, direct label-free biophysical readout technologies by means of electrophysiology have been developed. Planar patch-clamp electrophysiology provides a direct functional label-free readout of ion channel function in medium to high throughput. Further electrophysiology features, including temperature control and higher-throughput instruments, are continually being developed. Electrophysiological screening in a 384-well format has recently become possible. Advances in chip and microfluidic design, as well as in cell preparation and handling, have allowed challenging cell types to be studied by automated patch clamp. Assays measuring action potentials in stem cell-derived cardiomyocytes, relevant for cardiac safety screening, and neuronal cells, as well as a large number of different ion channels, including fast ligand-gated ion channels, have successfully been established by automated patch clamp. Impedance and multi-electrode array measurements are particularly suitable for studying cardiomyocytes and neuronal cells within their physiological network, and to address more complex physiological questions. This article discusses recent advances in electrophysiological technologies available for screening ion channel function and regulation.
authors.affiliation: a Nanion Technologies GmbH ; Munich , Germany.
authors.forename: Alison
authors.initials: A
authors.lastname: Obergrussberger
authors.affiliation: a Nanion Technologies GmbH ; Munich , Germany.
authors.forename: Sonja
authors.initials: S
authors.lastname: Stölzle-Feix
authors.affiliation: a Nanion Technologies GmbH ; Munich , Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Becker
authors.affiliation: a Nanion Technologies GmbH ; Munich , Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Brüggemann
authors.affiliation: a Nanion Technologies GmbH ; Munich , Germany.
authors.forename: Niels
authors.initials: N
authors.lastname: Fertig
authors.affiliation: b Albstadt-Sigmaringen University; Life Sciences Faculty ; Sigmaringen , Germany.
authors.forename: Clemens
authors.initials: C
authors.lastname: Möller
mesh_terms: D000818:Animals; D055808:Drug Discovery / Q000379:methods*; D057166:High-Throughput Screening Assays / Q000379:methods*; D006801:Humans; D018408:Patch-Clamp Techniques / Q000379:methods; D026902:Potassium Channel Blockers / Q000737:chemistry / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology*; D026941:Sodium Channel Blockers / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D026902:Potassium Channel Blockers; D054852:Small Molecule Libraries; D026941:Sodium Channel Blockers
keywords: Automated patch clamp; Electrophysiology; action potential; cardiomyocytes; impedance; ion channels; safety pharmacology; screening; temperature