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Patch Clamp Combined with Voltage/Concentration Clamp to Determine the Kinetics and Voltage Dependency of N-Methyl-d-aspartate (NMDA) Receptor Open Channel Blockers

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Patch-Clamp Methods and Protocols

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1183))

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Abstract

Electrophysiological techniques can be used to great effect to help determine the mechanism of action of a compound. However, many factors can compromise the resulting data and their analysis, such as the speed of solution exchange, expression of additional ion channel populations including other ligand-gated receptors and voltage-gated channels, compounds having multiple binding sites, and current desensitization and rundown. In this chapter, such problems and their solutions are discussed and illustrated using data from experiments involving the uncompetitive NMDA receptor antagonist memantine. Memantine differs from many other NMDA receptor channel blockers in that it is well tolerated and does not cause psychotomimetic effects at therapeutic doses. Various electrophysiological parameters of NMDA-induced current blockade by memantine have been proposed to be important in determining therapeutic tolerability; potency, onset and offset kinetics, and voltage dependency. These were all measured using whole cell patch clamp techniques using hippocampal neurons. Full results are shown here for memantine, and these are summarized and compared to those from similar experiments with other NMDA channel blockers. The interpretation of these results is discussed, as are theories concerning the tolerability of NMDA channel blockers, with the aim of illustrating how electrophysiological data can be used to form and support a physiological hypothesis.

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Author information

Authors and Affiliations

  1. Pharmacology, Non-Clinical Science, Merz Pharmaceuticals GmbH, Eckenheimer Landstraße 100, 60318, Frankfurt am Main, Germany

    Chris G. Parsons

  2. Charité-Universitätsmedizin, Berlin, Germany

    Kate E. Gilling

Authors
  1. Chris G. Parsons
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  2. Kate E. Gilling
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Corresponding author

Correspondence to Chris G. Parsons .

Editor information

Editors and Affiliations

  1. Department of Translational Bioscience, National Research Council of Canada, Ottawa, Ontario, Canada

    Marzia Martina

  2. Dept of Neuroscience & Brain Technologies, Italian Institute of Technology, Genoa, Italy

    Stefano Taverna

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Parsons, C.G., Gilling, K.E. (2014). Patch Clamp Combined with Voltage/Concentration Clamp to Determine the Kinetics and Voltage Dependency of N-Methyl-d-aspartate (NMDA) Receptor Open Channel Blockers. In: Martina, M., Taverna, S. (eds) Patch-Clamp Methods and Protocols. Methods in Molecular Biology, vol 1183. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-1096-0_3

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  • DOI: https://doi.org/10.1007/978-1-4939-1096-0_3

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-1095-3

  • Online ISBN: 978-1-4939-1096-0

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