Inhibition of IKs in guinea pig cardiac myocytes and guinea pig IsK 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 μmol/1). 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.