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 (I-ks) of the delayed rectifier (I-k) 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 (I-kr) of the delayed rectifier current (I-k). 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 (I-ks) of delayed rectifier, also blocks I-kr in a dose dependent manner. The steady state current at the end of a Is pulse (I-Is, step to +40 mV from a holding potential of -40 mV) was 1070.4+/-202.2 pA (n=5) and the tail current (I-tail) was 416.3+/-112.9 pA. Indapamide (750 mu M) reduced I-Is and I-tail to 254.5+/-62.3 pA and 42.2+/-37.7 pA respectively. Indapamide induced block was partially reversible for higher concentrations (greater than or equal to 750 mu M). (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.