Unit

UNIT 10.14 Measurement of Action Potential Generation in Isolated Canine Left Ventricular Midmyocardial Myocytes

  1. Daniel M. Johnson1,
  2. Leyla Hussein2,
  3. Roel L.H.M.G. Spätjens1,
  4. Jean-Pierre Valentin2,
  5. Paul G.A. Volders1,
  6. Najah Abi-Gerges2

Published Online: 1 DEC 2011

DOI: 10.1002/0471141755.ph1014s55

Current Protocols in Pharmacology

Current Protocols in Pharmacology

How to Cite

Johnson, D. M., Hussein, L., Spätjens, R. L., Valentin, J.-P., Volders, P. G. and Abi-Gerges, N. 2011. Measurement of Action Potential Generation in Isolated Canine Left Ventricular Midmyocardial Myocytes. Current Protocols in Pharmacology. 55:10.14:10.14.1–10.14.23.

Author Information

  1. 1

    Cardiovascular Research Institute Maastricht, Maastricht University Medical Centre, Maastricht, The Netherlands

  2. 2

    Safety Assessment UK, AstraZeneca R&D, Macclesfield, Cheshire, United Kingdom

Publication History

  1. Published Online: 1 DEC 2011
  2. Published Print: DEC 2011

Abstract

Proarrhythmic side effects are a major limitation during the drug development process for cardiac and non-cardiac compounds. Because changes in cardiac action potential (AP) are undesirable, the evaluation of the effects of test compounds on the AP is essential before advancing new compounds to clinical testing. However, an increase in repolarization duration alone is not always proarrhythmic, and newer surrogate markers have been suggested to better predict the occurrence of arrhythmia. Described in this unit is a protocol for assessing changes in AP duration in canine ventricular myocytes utilizing optical imaging techniques. This protocol can be used at an early stage of drug discovery due to its relatively fast throughput. Additionally, a protocol is presented for assessing the occurrence of after-depolarizations, as well as a novel parameter for proarrhythmic risk, beat-to-beat variability of repolarization. This protocol can be used at a later stage of the drug discovery process to assess proarrhythmic potential. Curr. Protoc. Pharmacol. 55:10.14.1-10.14.23. © 2011 by John Wiley & Sons, Inc.

Keywords:

  • left ventricular midmyocardial myocyte;
  • action potential;
  • nonclinical safety;
  • early after-depolarization;
  • QT interval prolongation;
  • arrhythmogenic potential