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.