Chromanol 293B inhibits slowly activating delayed rectifier and transient outward currents in canine left ventricular myocytes

Introduction: Drugs that selectively inhibit the slowly activating componen t of the delayed rectifier potassium current (I-Ks) are being considered as possible antiarrhythmic agents, because they produce more prolongation of action potential duration at fast rates with less transmural dispersion of repolarization compared with blockers of the rapidly activating component ( I-Kr), Although the chromanol derivative chromanol 293B has been shown to b e relatively selective in blocking I-Ks in some species, its selectivity is far from established. Methods and Results: The present study uses whole-cell, patch-clamp techniq ue to examine the selectivity of this compound for inhibition of I-Ks in co mparison with other repolarizing ionic currents, such as I-Kr, inward recti fier potassium current (I-K1), transient outward current (I-to), and L-type calcium current (ICa-L) in canine left ventricular mid-myocardial and endo cardial cells. Chromanol 293B blocked I-Ks with an IC50 of 1.8 muM and I-to with an IC50 of 38 muM. Concentrations as high as 30 muM did not affect I- K1, I-Kr, or ICa-L. Higher concentrations of chromanol 293B (100 muM) cause d a slight, but statistically insignificant, inhibition of I-Kr. Conclusion: Our results indicate that chromanol 293B is a relatively select ive blocker of I-Ks in canine left ventricular myocytes.