High throughput ion-channel pharmacology: planar-array-based voltage clamp.
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.
Kiss
Laszlo
L
Department of Molecular Pharmacology, Merck Research Laboratories, West Point, PA 19486, USA. laszlo_kiss@merck.com
Bennett
Paul B
PB
Uebele
Victor N
VN
Koblan
Kenneth S
KS
Kane
Stefanie A
SA
Neagle
Brad
B
Schroeder
Kirk
K
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
D027682:Cation Transport Proteins; D051638:Ether-A-Go-Go Potassium Channels; C092509:KCNH6 protein, human; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated