Shi, Hong, Hui-Zhen Wang, and Zhiguo Wang. Extracellular Ba21 blocks the cardiac transient outward K1 current. Am. J. Physiol. Heart Circ. Physiol. 278: H295–H299, 2000.—Ba21 is widely used as a tool in patch-clamp studies because of its ability to block a variety of K1 channels and to pass Ca21 channels. Its potential ability to block the cardiac transient outward K1 current (Ito) has not been clearly documented. We performed whole cell patch-clamp studies in canine ventricular and atrial myocytes. Extracellular application of Ba21 produced potent inhibition of Ito with an IC50 of ,40 μM. The effects were voltage independent, and the inactivation kinetics were not altered by Ba21. The potency of Ba21 was ,10 times higher than that of 4-aminopyridine (a selective Ito blocker with an IC50 of 430 μM) under identical conditions. By comparison, Ba21 blockade of the inward rectifier K1 current was voltage dependent; the IC50 was ,20 times lower (2.5 μM) than that for Ito when determined at 2100 mV and was comparable to Ito as determined at 260 mV (IC50 5 26 μM). Ba21 concentrations of #1 mM or higher failed to block ultrarapid delayed rectifier K1 current. Our data suggest that Ba21 can be considered a potent blocker of Ito.