Inhibition of I-Ks in guinea pig cardiac myocytes and guinea pig I-sK channels by the chromanol 293B

The chromanol derivative 293B was previously shown to inhibit a cAMP regulated K+ conductance in rat colon crypts. Subsequent studies on cloned K+ channels from the rat demonstrated that 293B blocks specifically I-sK channels expressed in Xenopus oocytes, but does not affect the delayed and inward rectifier Kv1.1 and KiR2.1, respectively. In the present study, the specificity of 293B for the cardiac K+ conductances I-Ks and I-Kr, and for the cloned guinea pig I-sK channel and the human HERG channel, which underly I-Ks and I-Kr, respectively, was analyzed. 293B inhibited both the slowly activating K+ conductance I-Ks in cardiac myocytes and guinea pig I-sK channels expressed in Xenopus oocytes with a similar IC50 (2-6 mu mol/l). In contrast, high concentrations of 293B had only a negligible effect on the more rapid activating I-Kr. Similarly, 293B exerted no effect on HERG channels expressed in Xenopus oocytes. In summary, 293B appears to be a rather specific inhibitor of I-Ks and the underlying I-sK channels.