Human stem cell-derived cardiomyocytes provide new models for studying the ion channel pharmacology of human cardiac cells for both drug discovery and safety pharmacology. Their utility will ultimately depend upon whether the detailed pharmacological profiles of their ion channels faithfully recapitulate those found in native myocytes. Kang et al. began an exploration of this area by surveying the pharmacology of the L-type Ca2+ channel in both induced pluripotent and embryonic stem cell-derived cardiomyocyte cell lines compared with native myocytes derived from guinea pig heart. The affinity for a wide range of structurally distinct antagonists is virtually identical in the stem cell-derived myocytes compared with the native cells. Conversely, Ca2+ channel activators, especially S-(−)-methyl 2,6-dimethyl-5-nitro-4-[2-(trifluoromethyl)phenyl]-1,4-dihydropyridine-3-carboxylate (Bay K 8644), failed to faithfully reproduce their established pharmacological effects in the stem cell-derived myocytes. The data point out the importance of detailed pharmacologic characterization of all ion channels in these and other stem cell-derived cell lines because these complex proteins contain multiple sites of drug action. With respect to L-type Ca2+ channels, Bay K 8644 and dimethyl-4-[2-(phenylmethyl)benzoyl]-1H-pyrrole-3-carboxylic acid methyl ester (FPL 64176) may represent a useful starting point when characterizing this channel's pharmacology in other stem cell-derived cell lines.
See article at J Pharmacol Exp Ther 2012, 341:510–517.
- Copyright © 2012 by The American Society for Pharmacology and Experimental Therapeutics