Ion channels screening

In order to fully appreciate the current advances in ion channel screening technologies, it is important to highlight some of the major discoveries that have directly or indirectly led to the current state in this field. The history of electrophysiology is rich and fascinating. It spans many different disciplines and fields (biology, physiology, biophysics, bioelectricity, etc.), extends over more than two centuries, and cannot be appropriately covered in this short review. Therefore, readers are referred to more comprehensive material on the subject matter [12-16]. 

Treherne, J.M. 2006. Exploiting high-throughput ion channel screening technologies in integrated drug discovery. Curr. Pharm. Des. 12, 397 -06. 

Uncertainty enters the equation with respect to either a drug s effect (IC ) or variability between experimental platforms, laboratories, cell types, and intra-animal/intraspe-eies differences. In a paper by Elkins et al. (2013), analysis of the typical variance in experimentally measured IC values of multiple ion channels at different laboratories allowed to determine when repeated ion channel screens should be performed to reduce uncertainty in a drug s action to acceptable levels to allow a meaningful interpretation of the data. While determination of the experimental uncertainty can be quantified, the uncertainty based on different... 

Elkins RC, Davies MR, Brough SJ, Gavaghan DJ, Cui Y, Abi-Gerges N, Mirams GR (2013). Variability in high-throughput ion-channel screening data and consequences for cardiac safety assessment. 7 P/ta/7naco/ Toxicol Methods 68 112-122. 

Farre C, Fertig N (Oct 2014). New strategies in ion channel screening for drug discovery are there ways to improve its productivity Expert Opin Drug Discov 9(10) 1103-1107. 

Mirams GR, Davies MR, Brough SJ, Bridgland-Taylor MH, Cui Y, Gavaghan DJ, Abi-Gerges N (Nov-Dec 2014). Prediction of Thorough QT study results using action potential simulations based on ion channel screens. J Pharmacol Toxicol Methods 70(3) 246-254. 

Beattie KA, Luscombe C, Williams G et al (2013) Evaluation of an in silico cardiac safety assay using ion channel screening data to predict QT interval changes in the rabbit ventricular wedge. J Pharmacol Toxicol Methods 68 88-96... 

Kenakin T, Christopoulos A (2012) Signalling bias in new drug discovery detection, quantification and therapeutic impact Nat Rev Drug Discov 12(3) 205-216 Kirsch G (2010) Mechanistic ion channel screening for drug discovery. Drug Discov Dev 13... 

Biological Applications Measuring membrane poten-tial HCN channel modulators BK channel activator " treating Alzheimer s disease antimicrobial susceptibility test ion channel screening assays hERG channel assay ... 

Wolff, C. Fuks, B. Chatelain, P. Comparative study of membrane potential-sensitive fluorescent probes and their use in ion channel screening assays. J. Biomol. Screening 2003, 8, 533-543. 

Biological Applications Measuring membrane potential ion channel screening assays taste modulators screening assays detecting cystic fibrosis transmembrane conductance regulator (CFTR) HCN channel modulators BK channel openers ... 

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