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Drug profiling using planar microelectrode arrays

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Abstract

Microelectrode arrays (MEAs) with evenly distributed multiple sensor spots have been designed for specific applications. Using the MEAs, we determined the relative profiles of potassium channel openers (KCOs) on cultured embryonic Sprague-Dawley rat cardiac myocytes. KCO, pinacidil (PIN), cromakalim (CROM), SDZ PCO400 (SDZ), or its vehicle, was added to the myocytes cumulatively. The action potential signal shapes in the presence of PIN and SDZ show that the changes in voltage over time and the magnitudes of the associated voltage change were reduced concentration-dependently. CROM affected sodium influx more than PIN and SDZ. The comparisons of changes in the rate of beating and propagation speed in the presence of KCOs were made using their corresponding pD2 values (the negative log of EC50). All KCOs caused concentration-dependent reductions in the rate of beating and propagation speed, with SDZ being the most potent. In addition to the signal shapes, rate of beating, and propagation speed, the origin of excitation and the excitation pattern inside the culture can be also extracted. The results show that the present system can differentiate the effects of different KCOs on myocytes. It might be possible to utilise the MEA as a means to classify drug action based upon a combined interpretation of the three different datasets gained from the extracellular recordings. The combination of these observations might be used as ‘drug signatures’ when profiling drugs in the future.

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Acknowledgements

This work was supported by an Earmarked Grant from the Research Grant Council of Hong Kong under contract no. 611205 and the Helmholtz Association of National Research Centres, Germany. The authors would like to thank N. Wolters (IBN-2, Electronic Workshop) and Y. Zhang (IBN-2) for their technical expertise in designing the current MEA system and M. Schindler (IBN-2) for the bandwidth characterisation. MEA chips were fabricated by M. Krause in a previous project at the Max Planck Institute for Polymer Research, Mainz, Germany within the group of W. Knoll.

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Authors and Affiliations

  1. Electronic and Computer Engineering, The University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China

    C. K. Yeung & M. Chan

  2. Institute of Bio- and Nanosystems - Bioelectronics (IBN-2) and CNI—Center of Nanoelectronic Systems for Information Technology, Forschungszentrum Jülich GmbH, 52425, Jülich, Germany

    F. Sommerhage, G. Wrobel, A. Offenhäusser & S. Ingebrandt

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  1. C. K. Yeung
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  2. F. Sommerhage
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  3. G. Wrobel
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  4. A. Offenhäusser
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  5. M. Chan
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  6. S. Ingebrandt
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Correspondence to S. Ingebrandt.

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Yeung, C.K., Sommerhage, F., Wrobel, G. et al. Drug profiling using planar microelectrode arrays. Anal Bioanal Chem 387, 2673–2680 (2007). https://doi.org/10.1007/s00216-007-1172-8

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  • DOI: https://doi.org/10.1007/s00216-007-1172-8

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