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19 Excitement over automated patch clamp: action potentials from stem cells and temperature effects on hERG inhibition
  1. A Haythornthwaite,
  2. S Stoelzle,
  3. C Haarmann,
  4. A Brüggemann,
  5. M George,
  6. N Fertig
  1. Nanion Technologies GmbH, Munich, Germany

Abstract

The hERG gene encodes a potassium channel responsible for the repolarisation of the IKr current in cardiac cells. Given the importance of this channel in the repolarisation of the cardiac action potential, and the disturbances of channel function by certain compounds such as anti-arrhythmias and anti-psychotics, this channel has become very important in safety pharmacology testing. Since some hERG-active compounds also exhibit different pharmacology at physiological temperature, experiments performed at this temperature are important in yielding more relevant data in safety screening. In this study, we describe the use of automated patch clamp electrophysiology for recording hERG stably transfected in HEK293 cells. Recordings of the hERG current from up to eight cells simultaneously could be performed at room temperature (RT) and at physiological temperature. Data will be shown for erythromycin which exhibited a higher potency at 35°C vs RT. Additionally, using a planar patch clamp workstation, recordings could be made from stem cell-derived cardiomyocytes. Currents mediated by K+, Na+ and Ca2+ channels could be recorded in the voltage clamp mode. What is more, action potentials in the current clamp mode could also be recorded and pharmacology was performed on action potentials (data will be shown). The use of stem cell-derived cardiomyocytes in safety testing is becoming increasingly important. The ability to test compounds on ion channels in both the voltage and the current clamp modes, as well as at different temperatures, may be crucial for future safety testing.

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