Indapamide blocks the rapid component of the delayed rectifier current in atrial tumor cells (AT-1 cells)

We studied the effects of a well known blocker (indapamide) of the slow component (Iks) of the delayed rectifier (Ik) on K+ currents in atrial tumor myocytes derived from transgenic mice (AT-1 cells) using one electrode voltage clamp method. These cells have been shown to express mRNAs encoding cardiac K+ channels and display a cardiac electrophysiological phenotype. The major K+ current is the rapid component (Ikr) of the delayed rectifier current (Ik). The purpose of this study was to show that a diuretic agent, indapamide, which was shown to be a selective blocker of the slow component (Iks) of delayed rectifier, also blocks Ikr in a dose dependent manner. The steady state current at the end of a 1s pulse (I1s, step to +40 mV from a holding potential of −40 mV) was 1070.4±202.2 pA (n=5) and the tail current (Itail) was 416.3±112.9 pA. Indapamide (750 μM) reduced I1s and Itail to 254.5±62.3 pA and 42.2±37.7 pA respectively. Indapamide induced block was partially reversible for higher concentrations (≥750 μM).