title: High throughput ion-channel pharmacology: planar-array-based voltage clamp.
abstract: Technological advances often drive major breakthroughs in biology. Examples include PCR, automated DNA sequencing, confocal/single photon microscopy, AFM, and voltage/patch-clamp methods. The patch-clamp method, first described nearly 30 years ago, was a major technical achievement that permitted voltage-clamp analysis (membrane potential control) of ion channels in most cells and revealed a role for channels in unimagined areas. Because of the high information content, voltage clamp is the best way to study ion-channel function; however, throughput is too low for drug screening. Here we describe a novel breakthrough planar-array-based HT patch-clamp technology developed by Essen Instruments capable of voltage-clamping thousands of cells per day. This technology provides greater than two orders of magnitude increase in throughput compared with the traditional voltage-clamp techniques. We have applied this method to study the hERG K(+) channel and to determine the pharmacological profile of QT prolonging drugs.
authors.affiliation: Department of Molecular Pharmacology, Merck Research Laboratories, West Point, PA 19486, USA. laszlo_kiss@merck.com
authors.forename: Laszlo
authors.initials: L
authors.lastname: Kiss
authors.forename: Paul B
authors.initials: PB
authors.lastname: Bennett
authors.forename: Victor N
authors.initials: VN
authors.lastname: Uebele
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Koblan
authors.forename: Stefanie A
authors.initials: SA
authors.lastname: Kane
authors.forename: Brad
authors.initials: B
authors.lastname: Neagle
authors.forename: Kirk
authors.initials: K
authors.lastname: Schroeder
mesh_terms: D000818:Animals; D016466:CHO Cells; D027682:Cation Transport Proteins / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000378:metabolism; D006224:Cricetinae; D064420:Drug-Related Side Effects and Adverse Reactions; D051638:Ether-A-Go-Go Potassium Channels; D006801:Humans; D015640:Ion Channel Gating; D018408:Patch-Clamp Techniques / Q000379:methods*; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated; D013678:Technology, Pharmaceutical
chemical_list: D027682:Cation Transport Proteins; D051638:Ether-A-Go-Go Potassium Channels; C092509:KCNH6 protein, human; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated