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The rapidly and slowly activating delayed rectifier K⁺ currents (I_Kr and I_Ks, respectively), which have different physiological properties, have been identified in cardiac cells from several species, including humans. Although expression of the minimal K⁺ channel protein (minK) cDNA in some systems results in a current resembling I_Ks, the role of this gene product in channel function remains controversial. In atrial tumor myocytes (AT-1 cells), no I_Ks is recorded, but minK mRNA is detected, raising the possibility that expression of the minK gene serves an as-yet-unidentified function. In these experiments, AT-1 cells were exposed to antisense oligonucleotides targeting the 5′ translation start site of the minK cDNA cloned from an AT-1 library. Cell size, I_Kr, and L-type and T-type Ca²⁺ currents were measured 24 to 48 hours after exposure and compared with data in cells exposed to the corresponding sense …