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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 +/- 26 micromol/L (at -60 mV) to 79 +/- 17 micromol/L (at -10 mV) for INa, from 174 +/- 19 micromol/L (at + 10 mV) to 98 +/- 7 micromol/L (at +60 mV) for Ito and from 148 +/- 28 micromol/L (at +10 mV) to 86 +/- 18 micromol/L (at +60 mV) for IKs. Significant inhibition was seen at concentrations as low as 10 micromol/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 micromol/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.

Effects of the Diuretic Agent Indapamide on Na + , Transient Outward, and Delayed Rectifier Currents in Canine Atrial Myocytes

Effects of the Diuretic Agent Indapamide on Na ⁺ , Transient Outward, and Delayed Rectifier Currents in Canine Atrial Myocytes