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 c-AMP 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/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.