The diuretic agent indapamide has been reported to block the slow component of the delayed rectifier K+ current(IKs)without altering the rapid component(IKr)or the inward rectifier current and has been used as a pharmacological probe for IKs; however,the effects of indapamide on Na+(INa),L-type Ca2+(ICa),and transient outward K+(Ito)currents have not been determined.We applied tight-seal,whole-cell,patch-clamp techniques to assess the effects of indapamide on INa,Ito,ICa,and IKs in canine atrial myocytes.Indapamide inhibited INa,Ito,and IKs in a concentration-dependent and reversible way,without altering ICa.Block increased with depolarization,with the 50% blocking concentration(EC50)decreasing from 129±26mmol/L (at -60 mV) to 79±17mmol/L (at -10mV) for INa,from 174±19mmol/L (at +10mV)to 98±7mmol/L (at＋60 mV)for Ito,and from 148±28 mmol/L (at＋10mV) to 86±18 mmol/L(at＋60 mV)for IKs.Significant inhibition was seen at concentrations as low as 10mmol/L for all 3 currents.In addition,indapamide effectively inhibited the ultrarapid delayed rectifier current in a voltage-independent way,with an EC50 of 138±7 mmol/L at＋10 mV.Standard microelectrode experiments showed the effects of indapamide on the action potential to be consistent with the ionic actions seen.We conclude that in addition to its well-recognized IKs-blocking action,indapamide also inhibits INa and Ito effectively and with similar potency.Thus,indapamide is not a reliable pharmacological probe with which to study the specific effects of IKs blockade,and INa and Ito block may contribute to the potential profile of cardiac actions of the compound.