Screening
trophysiology of stem cell-derived human car- diomyocytes (SCHCMs) and its usefulness in drug discovery and safety has been described. Extension of stem cell electrophysiology to other excitable tissues should greatly benefit the drug discovery effort (Figure 15).
Figure 16: GABAA channel activity in primary cortical neurons detected by Corning’s Epic® Label-free Technology
readouts. The protocols identify conformation- dependence of drug effects on voltage- and ligand- gated ion channels and can discriminate subtle dif- ferences in on- and off-target efficacy and safety. The hERG assay was a milestone delineating the importance of off-target effects on ion channels, since then cardiac channel profiling and traffick- ing have been introduced. More recently, the elec-
Figure 17 Cytocentrics CytoPatch™
Professional system for ultra- high data quality in automated patch clamping
Corning Label-free Epic® Technology (
www.corn-
ing.com/epic/) monitors the translocation of cellu- lar mass upon the activation of a target protein by using resonant waveguide sensors integrated into the bottom of 384-well microplates. This label-free detection technique is referred to as dynamic mass redistribution (DMR). The DMR signal is a novel quantifiable measurement and highly specific method of investigating GPCR targets. In recent years, the DMR methodology has been applied to ion channel targets with significant success for both recombinant systems (eg TRPV1-CHO, TRPA1-HEK293, P2RX1-CHO) and endogenous models (eg GABAA channel in primary cortical neurons and CRAC channel in HEK293 cells). Unlike traditional electrophysiological methods which focus on transportation of ions across the cell membrane, Epic ion channel assays focus on the translocation of large cellular molecules associ- ated with ion channel activity. Epic’s DMR response profiles could provide additional infor- mation about the functionality of ion channels and their activity modulators. For instance, research has demonstrated that DMR ion channel profiles were not only indicative of the specific activation and phosphorylation of ligand-gated ion channel Slack-B, but also provided more insight into the interaction between the ion channel and its regula- tory proteins4. Epic’s ability to detect more than the movements of ions across the cell membrane is helping researchers validate hypotheses about ion channels’ link to cell function and diseases. Label- free Epic Technology is available in a high- throughput screening platform from Corning and also Perkin Elmer’s Enspire® multi-mode bench- top unit. Corning also offers services including tar- get screening, compound profiling and assay devel- opment (Figure 16).
CytoPatch™ technology from Cytocentrics (
www.cytocentics.com) offers a new dimension in data quality in automated patch clamping. Both instruments, the CytoPatch™ Academic and the CytoPatch™ Professional, meet the demands of a flexible device with highest data quality. Moreover, the CytoPatch™ Professional is fully automated and suited for high throughput with several hours walk away time. The key to the high data quality is
52 Drug Discovery World Fall 2011
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