title: Indapamide blocks the rapid component of the delayed rectifier current in atrial tumor cells (AT-1 cells).
abstract: 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 1s pulse (I(1s), 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 microM) reduced I(1s) 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 (> or =750 microM).
authors.affiliation: Department of Anatomy and Physiology, Meharry Medical College, Nashville, TN 37208, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Kabir
authors.forename: M L
authors.initials: ML
authors.lastname: Bhattacharyya
authors.forename: T R
authors.initials: TR
authors.lastname: Robinson
mesh_terms: D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D004232:Diuretics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006325:Heart Atria / Q000166:cytology; D006329:Heart Conduction System / Q000187:drug effects*; D066298:In Vitro Techniques; D007190:Indapamide / Q000494:pharmacology*; D051379:Mice; D008822:Mice, Transgenic; D015221:Potassium Channels / Q000187:drug effects*; D014407:Tumor Cells, Cultured
chemical_list: D004232:Diuretics; D015221:Potassium Channels; D007190:Indapamide