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High-throughput electrophysiology: an emerging paradigm for ion-channel screening and physiology

Nature Reviews Drug Discovery volume 7, pages 358–368 (2008)Cite this article

Key Points

  • Ion channels represent an important class of druggable targets; however, it is generally appreciated in the field that ion-channel targeted drug discovery has been hampered by the unavailability of high-throughput platforms that use electrophysiological techniques for the characterization of compound activity. To address this bottleneck, in the past 5 years, several companies have developed and introduced automated platforms for performing electrophysiological studies.

  • This recent explosion includes different approaches taken to carry out multi-channel planar-array based patch-clamp recordings of mammalian cells, resulting in the commercialization of four systems — IonWorks, PatchXpress, Patchliner and CytoPatch. Complementary to these technologies has been the development of lower capacity systems that fully automate conventional manual patch-clamp recordings including the Flyscreen, AutoPatch and RoboPatch for mammalian cells, and the Robocyte and OpusXpress 6000A for Xenopus oocytes.

  • Despite the sophisticated technologies that are now available, automating patch-clamp electrophysiology often presents underestimated challenges regarding reproducibility with the cells being used; this needs to be fully appreciated when embarking on the implementation of any of these approaches.

  • The need to assess the potential of drug candidates to inhibit cardiac ion-channels, particularly hERG, has greatly contributed to the development of these technologies. Although higher throughput non-electrophysiological assays have a reasonable predictive potential, they have several limitations that might be technically or chemically limiting. Consequently, the desire to use electrophysiological assays early on to assess ion-channel liabilities has been one of the key drivers for implementation of automated electrophysiology.

  • Compound screening against molecularly isolated, heterologously expressed ion channels, will often identify drug candidates whose higher-order impact on networked neuronal systems are not necessarily inferable from their effects on individual conductances. Raising the throughput of pharmacological evaluation in such higher-order systems presents a distinct set of challenges. However, recent progress has been made in the development of automated systems for performing electrophysiogical studies in brain slices and other intact biological preparations.

  • The availability of these technologies has re-energized ion-channel targeted drug discovery by allowing the development of screening paradigms that were not feasible in the pre-automation era. In our opinion this holds much promise for the discovery and development of innovative new ion-channel targeted drugs. Tractability of ion channels as drug targets coupled with future advances in technology platforms and decreased cost of consumables are expected to support an even wider implementation of these automated systems.

Abstract

Ion channels represent highly attractive targets for drug discovery and are implicated in a diverse range of disorders, in particular in the central nervous and cardiovascular systems. Moreover, assessment of cardiac ion-channel activity of new chemical entities is now an integral component of drug discovery programmes to assess potential for cardiovascular side effects. Despite their attractiveness as drug discovery targets ion channels remain an under-exploited target class, which is in large part due to the labour-intensive and low-throughput nature of patch-clamp electrophysiology. This Review provides an update on the current state-of-the-art for the various automated electrophysiology platforms that are now available and critically evaluates their impact in terms of ion-channel screening, lead optimization and the assessment of cardiac ion-channel safety liability.

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Figure 1: Cross-section schematics of chips and flow channels used in automated electrophysiology platforms illustrate the diverse approaches taken.
Figure 2: Illustration of the various types of data obtained using hippocampal-slice field recordings.

References

  1. Overington, J. P., Al-Lazikani, B. & Hopkins, A. L. How many drug targets are there? Nature Rev. Drug Discov. 5, 993–996 (2006).

    CAS  Google Scholar 

  2. Imming, P., Sinning, C. & Meyer, A. Drugs, their targets and the nature and number of drug targets. Nature Rev. Drug Discov. 5, 821–834 (2006).

    CAS  Google Scholar 

  3. Owens, J. 2006 drug approvals: finding the niche. Nature Rev. Drug Discov. 6, 187–187 (2007).

    CAS  Google Scholar 

  4. Baxter, D. F. et al. A novel membrane potential-sensitive fluorescent dye improves cell-based assays for ion channels. J. Biomol. Screen. 7, 79–85 (2002).

    CAS  PubMed  Google Scholar 

  5. Benjamin, E. R. et al. State-dependent compound inhibition of Nav1.2 sodium channels using the FLIPR Vm dye: on-target and off-target effects of diverse pharmacological agents. J. Biomol. Screen. 11, 29–39 (2006).

    CAS  PubMed  Google Scholar 

  6. Lu, Q., Lin, S. & Dunlop, J. in Handbook of Assay Development in Drug Discovery. (ed. Minor, L. K.) 343–356 (CRC, Baco Raton, 2006).

    Google Scholar 

  7. Wolfe, C., Fuks, B. & Chatelain, P. Comparative study of membrane potential-sensitive fluorescent probes and their use in ion channel screening assays. J. Biomol. Screen. 8, 533–543 (2003).

    Google Scholar 

  8. Parihar, A. S. et al. Functional analysis of large conductance Ca2+-activated K+ channels: ion flux studies by atomic absorption spectrometry. Assay Drug Dev. Technol. 1, 647–654 (2003).

    CAS  PubMed  Google Scholar 

  9. Terstappen, G. C. Functional analysis of native and recombinant ion channels using a high-capacity nonradioactive rubidium efflux assay. Anal. Biochem. 272, 149–155 (1999).

    CAS  PubMed  Google Scholar 

  10. Terstappen, G. C. Nonradioactive rubidium ion efflux assay and its applications in drug discovery and development. Assay Drug Dev. Technol. 2, 553–559 (2004).

    CAS  PubMed  Google Scholar 

  11. Pan, Y. P., Xu, X. H. & Wang, X. L. High throughput screening method of potassium channel regulators. Yao Xue Xue Bao 39, 85–88 (2004) (in Chinese).

    CAS  PubMed  Google Scholar 

  12. Hamill, O. P., Marty, A., Neher, E., Sakmann, B. & Sigworth, F. J. Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Arch. 391, 85–100 (1981).

    CAS  PubMed  Google Scholar 

  13. Asmild, M. et al. Upscaling and automation of electrophysiology: toward high throughput screening in ion channel drug discovery. Recept. Channels 9, 49–58 (2003).

    CAS  PubMed  Google Scholar 

  14. Lepple-Wienhues, A., Ferlinz, K., Seeger, A. & Schafer, A. Flip the tip: an automated, high quality, cost-effective patch clamp screen. Recept. Channels 9, 13–17 (2003).

    CAS  PubMed  Google Scholar 

  15. Vasilyev, D. V., Merrill, T. L. & Bowlby, M. R. Development of a novel automated ion channel recording method using “inside-out” whole-cell membranes. J. Biomol. Screen. 10, 806–813 (2005).

    CAS  PubMed  Google Scholar 

  16. Vasylyev, D., Merrill, D., Iwanow, A., Dunlop, J. & Bowlby, M. A novel method for patch clamp automation. Pflugers Arch. 452, 240–247 (2006).

    Google Scholar 

  17. Schnizler, K., Kuster, M., Methfessel, C. & Fejtl, M. The roboocyte: automated cDNA/mRNA injection and subsequent TEVC recording on Xenopus oocytes in 96-well microtiter plates. Recept. Channels 9, 41–48 (2003).

    CAS  PubMed  Google Scholar 

  18. Papke, R. L. Estimation of both the potency and efficacy of α7 nAChR agonists from single-concentration responses. Life Sci. 78, 2812–2819 (2006).

    CAS  PubMed  Google Scholar 

  19. Kiss, L. et al. High throughput ion-channel pharmacology: planar-array-based voltage clamp. Assay Drug Dev. Technol. 1, 127–135 (2003).

    CAS  PubMed  Google Scholar 

  20. Schroeder, K., Neagle, B., Trezise, D. J. & Worley, J. Ionworks HT: a new high-throughput electrophysiology measurement platform. J. Biomol. Screen. 8, 50–64 (2003). This represents the first validation of an approach to the full automation of patch clamping in mammalian cells using a perforated patch-clamp format.

    CAS  PubMed  Google Scholar 

  21. Sorota, S., Zhang, X. S., Margulis, M., Tucker, K. & Priestley, T. Characterization of a hERG screen using the IonWorks HT: comparison to a hERG rubidium efflux screen. Assay Drug Dev. Technol. 3, 47–57 (2005).

    CAS  PubMed  Google Scholar 

  22. Bridgland-Taylor, M. H. et al. Optimisation and validation of a medium-throughput electrophysiology-based hERG assay using IonWorks HT. J. Pharmacol. Toxicol. Methods 54, 189–199 (2006).

    CAS  PubMed  Google Scholar 

  23. Finkel, A. et al. Population patch clamp improves data consistency and success rates in the measurement of ionic currents. J. Biomol. Screen. 11, 488–496 (2006). Describes the second-generation innovation in the IonWorks platform incorporating the population patch-clamp mode resulting in a significant increase in percentage success rate and compound throughput.

    CAS  PubMed  Google Scholar 

  24. John, V. H. et al. Novel 384-well population patch clamp electrophtsiology assays for Ca2+-activated K+ channels. J. Biomol. Screen. 12, 50–60 (2007).

    CAS  PubMed  Google Scholar 

  25. Tao, H. et al. Automated tight seal electrophysiology for assessing the potential hERG liability of pharmaceutical compounds. Assay Drug Dev. Technol. 2, 497–506 (2004). Original study on the implementation of automated electrophysiology in support of preclinical evaluation of cardiac ion-channel liability of drug candidates.

    CAS  PubMed  Google Scholar 

  26. Xu, J. et al. A benchmark study with sealchip planar patch-clamp technology. Assay Drug Dev. Technol. 1, 675–684 (2003). The first demonstration of automated patch clamp in mammalian cells achieving the same giga-ohm quality seals to those in manual patch-clamp electrophysiology.

    CAS  PubMed  Google Scholar 

  27. Mathes, C. QPatch: the past, present and future of automated patch clamp. Expert Opin. Ther. Targets 10, 319–327 (2006).

    CAS  PubMed  Google Scholar 

  28. Dubin, A. E. et al. Identifying modulators of hERG channel activity using the PatchXpress planar patch clamp. J. Biomol. Screen. 10, 168–181 (2005).

    CAS  PubMed  Google Scholar 

  29. Guo, L. & Guthrie, H. Automated electrophysiology in the preclinical evaluation of drugs for potential QT prolongation. J. Pharmacol. Toxicol. Methods 52, 123–135 (2005).

    CAS  PubMed  Google Scholar 

  30. Kutchinsky, J. et al. Characterization of potassium channel modulators with QPatch automated patch-clamp technology: system characteristics and performance. Assay Drug Dev. Technol. 1, 685–693 (2003).

    CAS  PubMed  Google Scholar 

  31. Farre, C. et al. Automated ion channel screening: patch clamping made easy. Expert Opin. Ther. Targets 11, 557–565 (2007).

    CAS  PubMed  Google Scholar 

  32. Brueggemann, A. et al. Ion channel drug discovery and research: the automated Nano-Patch-Clamp technology. Curr. Drug Discov. Technol. 1, 91–96 (2004).

    CAS  PubMed  Google Scholar 

  33. Bruggemann, A. et al. High quality ion channel analysis on a chip with the NPC technology. Assay Drug Dev. Technol. 1, 665–673 (2003).

    CAS  PubMed  Google Scholar 

  34. Stett, A., Burkhardt, C., Weber, U., van Stiphout, P. & Knott, T. CYTOCENTERING: a novel technique enabling automated cell-by-cell patch clamping with the CYTOPATCH chip. Recept. Channels 9, 59–66 (2003).

    CAS  PubMed  Google Scholar 

  35. Groot-Kormelink, P. J., Tranter, P. R. & Gosling, M. Maximising the efficiency and application of automated planar patch clamp electrophysiology. Eur. Pharm. Rev. 1, 39–45 (2007).

    Google Scholar 

  36. Jow, F. et al. Validation of a medium-throughput electrophysiological assay for KCNQ2/3 channel enhancers using IonWorks HT. J. Biomol. Screen. 12, 1059–1067 (2007).

    CAS  PubMed  Google Scholar 

  37. Virginio, C., Giacometti, A., Aldegheri, L., Rimland, J. M. & Terstappen, G. C. Pharmacological properties of rat α7 nicotinic receptors expressed in native and recombinant cell systems. Eur. J. Pharmacol. 445, 153–161 (2002).

    CAS  PubMed  Google Scholar 

  38. Williams, M. E. et al. Ric-3 promotes functional expression of the nicotinic acetylcholine receptor α7 subunit in mammalian cells. J. Biol. Chem. 280, 1257–1263 (2005).

    CAS  PubMed  Google Scholar 

  39. Kola, I. & Landis, J. Can the pharmaceutical industry reduce attrition rates? Nature Rev. Drug Discov. 3, 711–715 (2004).

    CAS  Google Scholar 

  40. Kramer, J., Sagartz, J. & Morris, D. The application of discovery toxicology and pathology towards the design of safer pharmaceutical lead candidates. Nature Rev. Drug Discov. 6, 636–649 (2007).

    CAS  Google Scholar 

  41. Preziosi, P. Science, pharmacoeconomics and ethics in drug R.&D: a sustainable future scenario? Nature Rev. Drug Discov. 3, 521–526 (2004).

    CAS  Google Scholar 

  42. Redfern, W. S. et al. Relationships between preclinical cardiac electrophysiology, clinical QT interval prolongation and torsade de pointes for a broad range of drugs: evidence for a provisional safety margin in drug development. Cardiovasc. Res. 58, 32–45 (2003). A seminal study defining the relationships between preclinical ion-channel pharmacology and potential for QT interval prolongation in a diverse range of drug molecules.

    CAS  PubMed  Google Scholar 

  43. Sanguinetti, M. C. & Tristani-Firouzi, M. hERG potassium channels and cardiac arrhythmia. Nature 440, 463–469 (2006).

    CAS  PubMed  Google Scholar 

  44. International Conference on Harmonisation (ICH). Guidance for Industry. S7B Nonclinical Evaluation of the Potential for Delayed Ventricular Repolarization (QT Interval Prolongation) by Human Pharmaceuticals. ICH web site [online], (2005).

  45. Bass, A. S., Tomaselli, G., Bullingham, R. 3rd & Kinter, L. B. Drugs effects on ventricular repolarization: a critical evaluation of the strengths and weaknesses of current methodologies and regulatory practices. J. Pharmacol. Toxicol. Methods 52, 12–21 (2005).

    CAS  PubMed  Google Scholar 

  46. Friedrichs, G. S., Patmore, L. & Bass, A. Non-clinical evaluation of ventricular repolarization (ICH S7B): results of an interim survey of international pharmaceutical companies. J. Pharmacol. Toxicol. Methods 52, 6–11 (2005).

    CAS  PubMed  Google Scholar 

  47. Aronov, A. M. Common pharmacophores for uncharged human ether-a-go-go-related gene (hERG) blockers. J. Med. Chem. 49, 6917–6921 (2006).

    CAS  PubMed  Google Scholar 

  48. Dubus, E., Ijjaali, I., Petitet, F. & Michel, A. In silico classification of HERG channel blockers: a knowledge-based strategy. ChemMedChem 1, 622–630 (2006).

    CAS  PubMed  Google Scholar 

  49. Song, M. & Clark, M. Development and evaluation of an in silico model for hERG binding. J. Chem. Inf. Model. 46, 392–400 (2006).

    CAS  PubMed  Google Scholar 

  50. Finlayson, K., Turnbull, L., January, C. T., Sharkey, J. & Kelly, J. S. [3H]dofetilide binding to HERG transfected membranes: a potential high throughput preclinical screen. Eur. J. Pharmacol. 430, 147–148 (2001).

    CAS  PubMed  Google Scholar 

  51. Deacon, M. et al. Early evaluation of compound QT prolongation effects: a predictive 384-well fluorescence polarization binding assay for measuring hERG blockade. J. Pharmacol. Toxicol. Methods 55, 238–247 (2007).

    CAS  PubMed  Google Scholar 

  52. Guthrie, H., Livingston, F. S., Gubler, U. & Garippa, R. A place for high-throughput electrophysiology in cardiac safety: screening hERG cell lines and novel compounds with the ion works HTTM system. J. Biomol. Screen. 10, 832–840 (2005).

    CAS  PubMed  Google Scholar 

  53. Meyer, T., Boven, K. H., Gunther, E. & Fejtl, M. Micro-electrode arrays in cardiac safety pharmacology: a novel tool to study QT interval prolongation. Drug Saf. 27, 763–772 (2004).

    CAS  PubMed  Google Scholar 

  54. Meyer, T., Leisgen, C., Gonser, B. & Gunther, E. QT-screen: high-throughput cardiac safety pharmacology by extracellular electrophysiology on primary cardiac myocytes. Assay Drug Dev. Technol. 2, 507–514 (2004).

    CAS  PubMed  Google Scholar 

  55. Bliss, T. & Lomo, T. Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path. J. Physiol. 232, 331–356 (1973). Original demonstration of the synaptic property of LTP, a widely studied cellular model of memory, and now a recent focus of automation efforts in brain-slice electrophysiology.

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Madison, D., Malenka, R. & Nicoll, R. Mechanisms underlying long-term potentiation of synaptic transmission. Ann. Rev. Neurosci. 14, 379–397 (1991).

    CAS  PubMed  Google Scholar 

  57. Bliss, T. & Collingridge, G. A synaptic model of memory: long-term potentiation in the hippocampus. Nature 361, 31–39 (1993).

    CAS  PubMed  Google Scholar 

  58. Nicoll, R. & Malenka, R. Expression mechanisms underlying NMDA receptor-dependent long-term potentiation. Ann. NY Acad. Sci. 868, 515–525 (1999).

    CAS  PubMed  Google Scholar 

  59. Kemp, N. & Bashir, Z. Long-term depression: a cascade of induction and expression mechanisms. Prog. Neurobiol. 65, 339–365 (2001).

    CAS  PubMed  Google Scholar 

  60. Lynch, M. Long-term potentiation and memory. Physiol. Rev. 84, 87–136 (2004).

    CAS  PubMed  Google Scholar 

  61. Larson, J., Lynch, G., Games, D. & Seubert, P. Alterations in synaptic transmission and long-term potentiation in hippocampal slices from young and aged PDAPP mice. Brain Res. 840, 23–35 (1999).

    CAS  PubMed  Google Scholar 

  62. Jacobsen, J. et al. Early-onset behavioral and synaptic deficits in a mouse model of Alzheimer's disease. Proc. Natl Acad. Sci. USA 103, 5161–5166 (2006).

    CAS  PubMed  Google Scholar 

  63. Picconi, B. et al. Pathological synaptic plasticity in the striatum: implications for Parkinson's disease. Neurotoxicology 26, 779–783 (2005).

    CAS  PubMed  Google Scholar 

  64. Kreitzer, A. & Malenka, R. Endocannabinoid-mediated rescue of striatal LTD and motor deficits in Parkinson's disease models. Nature 445, 643–647 (2007).

    CAS  PubMed  Google Scholar 

  65. Coyle, J. Glutamate and schizophrenia: beyond the dopamine hypothesis. Cell. Mol. Neurobiol. (2006).

  66. Stephan, K., Baldeweg, T. & Friston, K. Synaptic plasticity and dysconnection in schizophrenia. Biol. Psychiatry 59, 929–939 (2006).

    CAS  PubMed  Google Scholar 

  67. McIlWain, H. Praparing Neural Tissues for Metabolic Study in Isolation (ed. McIlWain, H.) (Churchill Livingstone, Edinburgh, London & New York, 1975).

    Google Scholar 

  68. Teyler, T. Brain slice preparation: hippocampus. Brain Res. Bull. 5, 391–403 (1980).

    CAS  PubMed  Google Scholar 

  69. Andersen, P. Brain slices — a neurobiological tool of increasing usefulness. Trends Neurosci. 4, 53–56 (1981).

    Google Scholar 

  70. Dingledine, R. Brain Slices (ed. Dingledine, R.) (Springer, New York, 1984).

    Google Scholar 

  71. Stopps, M. et al. Design and application of a novel brain slice system that permits independent electrophysiological recordings from multiple slices. J. Neurosci. Methods 132, 137–148 (2004).

    CAS  PubMed  Google Scholar 

  72. Huang, C.-W., Hsieh, Y.-J., Tsai, J. & Huang, C.-C. Effects of lamotrigine on field potentials, propagation, and long-term potentiation in rat prefrontal cortex in multi-electrode recording. J. Neurosci. Res. 83, 1141–1150 (2006).

    CAS  PubMed  Google Scholar 

  73. Krause, M. & Jia, Y. Serotonergic modulation of carbachol-induced rhythmic activity in hippocampal slices. Neuropharmacology 48, 381–390 (2005).

    CAS  PubMed  Google Scholar 

  74. Oka, H., Shimono, K., Ogawa, R., Sugihara, H. & Taketani, M. A new planar multielectrode array for extracellular recording: application to hippocampal acute slice. J. Neurosci. Methods 93, 61–67 (1999).

    CAS  PubMed  Google Scholar 

  75. Shimono, K., Baudry, M., Panchenko, V. & Taketani, M. Chronic multichannel recordings from organotypic hippocampal slice cultures: protection from excitotoxic effects of NMDA by noncompetitive NMDA antagonists. J. Neurosci. Methods 120, 193–202 (2002).

    CAS  PubMed  Google Scholar 

  76. Shimono, K., Brucher, F., Granger, R., Lynch, G. & Taketani, M. Origins and distribution of cholinergically induced beta rhythms in hippocampal slices J. Neurosci. 20, 8462–8473 (2000).

    CAS  PubMed  Google Scholar 

  77. Egert, U. et al. A novel organotypic long-term culture of the rat hippocampus on substrate-integrated multielectrode arrays. Brain Res. Protocols 2, 229–242 (1998).

    CAS  Google Scholar 

  78. Martinoia, S. et al. In vitro cortical neuronal networks as a new high-sensitive system for biosensing applications. Biosens. Bioelectron. 20, 2071–2078 (2005).

    CAS  PubMed  Google Scholar 

  79. Potter, S. & DeMarse, T. A new approach to neural cell culture for long-term studies. J. Neurosci. Methods 110, 17–24 (2001).

    CAS  PubMed  Google Scholar 

  80. van Pelt, J., Corner, M., Wolters, P., Rutten, W. & Ramakers, G. Longterm stability and developmental changes in spontaneous network burst firing patterns in dissociated rat cerebral cortex cell cultures on microeloectrode arrays. Neurosci. Lett. 361, 86–89 (2004).

    CAS  PubMed  Google Scholar 

  81. Morin, F., Takamura, Y. & Tamiya, E. Investigating neuronal activity with planar microelectrode arrays: achievements and new perspectives. J. Biosci. Bioeng. 100, 131–143 (2005).

    CAS  PubMed  Google Scholar 

  82. van Pelt, J., Vajda, I., Wolters, P., Corner, M. & Ramakers, G. Dynamics and plasticity in developing neuronal networks in vitro. Prog. Brain Res. 147, 173–188 (2005).

    PubMed  Google Scholar 

  83. Wagenaar, D., Madhavan, R., Pine, J. & Potter, S. Controlling bursting in cortical cultures with closed-loop multi-electrode stimulation. J. Neurosci. 25, 680–688 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Stacy, R., Demas, J., Burgess, R., Sanes, J. & Wong, R. Disruption and recovery of patterned retinal activity in the absence of acetylcholine. J. Neurosci. 25, 9347–9357 (2005).

    CAS  PubMed  Google Scholar 

  85. Ishikane, H., Gangi, M., Honda, S. & Tachibana, M. Synchronized retinal oscillations encode essential information for escape behavior in frogs. Nature Neurosci. 8, 1087–1095 (2005).

    CAS  PubMed  Google Scholar 

  86. Haraguchi, Y., Shimizu, T., Yamato, M., Kikuchi, A. & Okano, T. Electrical coupling of cardiomyocyte sheets occurs rapidly via functional gap junction formation. Biomaterials 27, 4765–4774 (2006).

    CAS  PubMed  Google Scholar 

  87. Reppel, M., Boettinger, C. & Hescheler, J. β-Adrenergic and muscarinic modulation of human embryonic stem cell-derived cardiomyocytes. Cell Physiol. Biochem. 14, 187–196 (2004).

    CAS  PubMed  Google Scholar 

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Acknowledgements

The authors thank A. Randall for comments on review.

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  1. Neuroscience Discovery Research, Wyeth Research, CN-8000, Princeton, 08543, New Jersey, USA

    John Dunlop, Mark Bowlby, Ravikumar Peri, Dmytro Vasilyev & Robert Arias

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Glossary

Faraday cage

An enclosure for blocking out external static electrical fields, made from a conducting material. It is named after the nineteenth-century physicist Michael Faraday.

IC50

The half maximal inhibitory concentration. This represents the concentration of an inhibitor that is required for 50% inhibition of a biological or molecular process.

Z′ values

A measurement that takes into account the dynamic range of the assay (how far apart the positive controls are from the negative controls), as well as data variability (how much variation is seen in the measurements of positive and negative controls).

Fluorescence-activated cell sorter

(FACS). A machine that can rapidly separate cells in suspension on the basis of size and the colour of their fluorescence.

ICH regulations

International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The ICH works to bring together government regulators and drug industry representatives from the United States, the European Union and Japan to make the international drug regulatory process more efficient and uniform.

Long-term potentiation

(LTP). The prolonged strengthening of synaptic communication, which is induced by high-frequency patterned input and is thought to be involved in learning and memory formation.

Long-term depression

(LTD). An enduring weakening of synaptic strength that is thought to interact with long-term potentiation (LTP) in the cellular mechanisms of learning and memory in structures such as the hippocampus and cerebellum. Unlike LTP, which is produced by brief high-frequency stimulation, LTD can be produced by long-term, low-frequency stimulation.

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Dunlop, J., Bowlby, M., Peri, R. et al. High-throughput electrophysiology: an emerging paradigm for ion-channel screening and physiology. Nat Rev Drug Discov 7, 358–368 (2008). https://doi.org/10.1038/nrd2552

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