Clofilium-induced block of delayed rectifier type K+ current in atrial tumor cells (AT-1 cells).
Atrial tumor myocytes derived from transgenic mice (AT-1 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 of the delayed rectifier (I(kr)). The purpose of the study was to characterize the mode of action of a class III anti-arrhythmic agent (C3A), clofilium, in these cells to elucidate further the mechanism and functional consequence of block. We show that clofilium blocks this I(kr) in a dose-dependent manner with IC50 of 1.25 microM. Clofilium induced block was irreversible for higher concentrations (> or = 50 microM) and partially reversible for lower doses. The reversal potential for this current was -77.5+/-1.5 mV. The block is voltage dependent and the drug probably binds the channel in the open state.
Bhattacharyya
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Department of Physiology, Meharry Medical College, Nashville, TN 37208, USA.
Sarker
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Mull
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Debnam
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D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D005260:Female; D006325:Heart Atria; D006338:Heart Neoplasms / Q000473:pathology / Q000503:physiopathology*; D007811:Lanthanum / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology*; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000889:Anti-Arrhythmia Agents; D026902:Potassium Channel Blockers; D000644:Quaternary Ammonium Compounds; D007811:Lanthanum; C022799:clofilium