Application of PatchXpress Planar Patch Clamp Technology to the Screening of New Drug Candidates for Cardiac KCNQ1/KCNE1 (I Ks) Activity

A cardiac safety concern for QT prolongation and potential for pro-arrhythmia exists due to inhibition of the cardiac slowly activating delayed rectifier potassium current, IKs. Selective inhibitors of IKs have been shown to prolong the QT interval in animal models. On the other hand, IKs has been considered as a target for anti-arrhythmic therapy due to certain biophysical and pharmacological properties and its expression pattern in the heart. Consequently, we have developed a method utilizing a human embryonic kidney (HEK)-293 cell line expressing KCNQ1/KCNE1 (genes that encode for the IKs channel) as a model for screening of new compounds for IKs activity. This study was designed (1) to establish and optimize the experimental conditions for measurement of IKs using PatchXpress™ 7000A (Molecular Devices Corporation, Sunnyvale, CA) and (2) to test the effects of IKs inhibitors and compare the 50% inhibitory concentration (IC50) values determined with PatchXpress versus conventional patch clamp in order t...