Block by propofol and thiopentone of the min K current (IsK) expressed in Xenopus oocytes

The slowly activating component of the delayed rectifier potassium current (IKs) in the heart is important during the repolarization of the cardiac action potential. Injection into Xenopus oocytes of mRNA coding for the min K protein induces a similar current (IsK) and recent observations support the hypothesis that functional channels result from the association of the min K protein with an endogenous K+ channel similar to the recently cloned KvLQT1. The general anaesthetics propofol and thiopentone have been shown to suppress cardiac IKs with no effect on the rapidly activating component of IK (Takahashi and Terrar 1995). It was therefore of interest to test whether IsK was also inhibited by propofol and thiopentone. IsK was induced following injection into oocytes of min K mRNA which was transcribedin vitro from a synthetic gene (Hausdorff et al. 1991). IsK was activated by step depolarizations to a series of potentials from a holding potential of –40mV and measured as the deactivating tail current on repolarization to the holding potential. Following a 2s depolarization to +45mV, propofol and thiopentone caused concentration-dependent reductions in IsK. The estimated IC50 value for the block of IsK by propofol was 250 μΜ and by thiopentone was 56 μΜ. Block of IsK by both propofol and thiopentone was not dependent on voltage or time. The reductions in IsK caused by propofol and thiopentone are consistent with the previously reported effects of these anaesthetics on IKs in the heart and support the hypothesis that the min K protein contributes to the molecular basis of the cardiac IKs channel.