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  • CiPA hERG Protocol

    This protocol was used for hERG studies on the Patchliner and SyncroPatch 384PE.

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    Effects of Cisapride using the CiPA hERG protocol on the SyncroPatch 384PE

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    CiPA-specified cardiac ion channels recorded at high throughput

  • Gigaseal HTS patch clamp

    High throughput recordings of cardiac ion channels at physiological temperature

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    CardioExcyte 96 with integrated liquid handling for cardiac safety screening

hERG - "Effect of temperature on erythromycin action on hERG currents recorded on Nanion's Patchliner"

icon pl   Patchliner application note:   logo pdf   (0.9 MB)
Cells were kindly provided by Millipore.

Summary:

The hERG gene encodes a potassium channel responsible for the repolarization of the IKr current in cardiac cells (Sanguinetti et al, 1995). This channel is important in the repolarization of the cardiac action potential. Abnormalities in this channel can lead to long or short QT syndrome, leading to potentially fatal cardiac arrhythmia. Given the importance of this channel in maintaining cardiac function, and disturbances of channel activity by certain compounds such as anti-arrhythmias and anti-psychotics, it has become an important target in compound safety screening. Compounds can display different properties or different potencies at physiological temperature (35°C) vs. room temperature (RT) and therefore, it is a desirable option to be able to study this channel electrophysiologically at elevated temperature. One such compound which has been shown to have an increase in potency at physiological temperature is erythromycin. Erythromycin is a macrolide antibiotic which can cause QT prolongation and cardiac arrhythmia. Erythromycin has been shown to block hERG channels at physiological temperature with an IC50 of approximately 40 mM (Stanat et al, 2003; Duncan et al, 2005). However, at RT erythromycin is much less potent. At a concentration of 100 mM, erythromycin causes no significant block of hERG currents at RT but significantly blocks currents at physiological temperature (Guo et al, 2005). Here we present data collected on an 8-channel Patchliner with temperature control at RT and at 35°C and the effect this has on the potency of erythromycin.

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