A novel enhancing effect of clofilium on transient outward-type cloned cardiac K+ channel currents.

1. The antiarrythmic drug, clofilium, has been shown to block several types of K+ channel currents. To investigate the effects of clofilium on the transient outward K+ current (Ito), a cloned Ito-type cardiac K+ channel (RHK1) was expressed in Xenopus oocytes and the drug effects were examined on whole cell currents. 2. Extracellular application of clofilium slightly inhibited the current at +60 mV from a holding potential of -80 mV. However, it unexpectedly enhanced the current from a holding potential of -60 mV in a dose-dependent manner (219 +/- 39% of control at 100 microM). 3. This enhancement is probably due to an increase in the ratio of channels in the resting state during steady depolarization, since clofilium shifted the inactivation curve in the depolarizing direction. 4. LY97119, a tertiary ammonium analogue of clofilium, did not exhibit this enhancing effect but only inhibited the current. 5. Clofilium may be useful for the study of channel inactivation because this type of phenomenon has not been reported for any other drug.