Cardiac ion channel modulation by the hypoglycaemic agent rosiglitazone

The hypoglycaemic thiazolidinedione rosiglitazone is used clinically in the treatment of type 2 diabetes. However, in 2010, information relating to rosiglitazone‐associated increased cardiovascular risk led the European Medicines Agency to recommend suspension of marketing authorizations for rosiglitazone‐containing anti‐diabetes drugs, while the US Food and Drug Administration recommended significant restriction on the agent's use. Two timely studies in this issue of the British Journal of Phrarmacology provide new information regarding modification of cardiac cellular electrophysiology by rosiglitazone. Szentandrássy et al. demonstrate canine ventricular action potential modification and concentration‐dependent suppression of L‐type Ca current and of transient outward and rapid delayed rectifier K currents. Jeong et al. demonstrate concentration‐dependent inhibition of recombinant Kv4.3 channels, providing mechanistic insight into the likely molecular basis of transient outward K current inhibition by the compound. Further studies using diabetic models would be of value to determine whether, in a diabetic setting, rosiglitazone modification of these channels could affect the risk of arrhythmia at clinically relevant drug concentrations. LINKED ARTICLES This article is a commentary on Szentandrássy et al., pp. 499–509 of this issue and Jeong et al., pp. 510–520 of this issue. To view these papers visit http://dx.doi.org/10.1111/j.1476‐5381.2011.01215.x and http://dx.doi.org/10.1111/j.1476‐5381.2011.01210.x