Cross-Site and Cross-Platform Variability of Automated Patch Clamp Assessments of Drug Effects on Human Cardiac Currents in Recombinant Cells

  • Publication Date :
  • Publication Type : Journal Article
  • Author(s) : Kramer J, Himmel HM, Lindqvist A, Stoelzle-Feix S, Chaudhary KW, Li D, Bohme GA, Bridgland-Taylor M, Hebeisen S, Fan J, Renganathan M, Imredy J, Humphries ESA, Brinkwirth N, Strassmaier T, Ohtsuki A, Danker T, Vanoye C, Polonchuk L, Fermini B, Pierson JB, & Gintant G
  • Journal Name : Nature Scientific Reports

Automated patch clamp (APC) instruments enable efficient evaluation of electrophysiologic effects of drugs on human cardiac currents in heterologous expression systems. Differences in experimental protocols, instruments, and dissimilar site procedures affect the variability of IC50 values characterizing drug block potency. This impacts the utility of APC platforms for assessing a drug’s cardiac safety margin. We determined variability of APC data from multiple sites that measured blocking potency of 12 blinded drugs (with different levels of proarrhythmic risk) against four human cardiac currents (hERG [IKr], hCav1.2 [L-Type ICa], peak hNav1.5, [Peak INa], late hNav1.5 [Late INa]) with recommended protocols (to minimize variance) using five APC platforms across 17 sites.

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