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

The slowly activating component of the delayed rectifier potassium current (I-Ks) 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 (I-sK) 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 I-Ks with no effect on the rapidly activating component of I-K (Takahashi and Terrar 1995). It was therefore of interest to test whether I-sK was also inhibited by propofol and thiopentone. I-sK was induced following injection into oocytes of min K mRNA which was transcribed in vitro from a synthetic gene (Hausdorff et al. 1991). I-sK was activated by step depolarizations to a series of potentials from a holding potential of -40 mV and measured as the deactivating tail current on repolarization to the holding potential. Following a 2 s depolarization to +45 mV, propofol and thiopentone caused concentration-dependent reductions in I-sK The estimated IC50 value for the block of I-sK by propofol was 250 mu M and by thiopentone was 56 mu M. Block of I-sK by both propofol and thiopentone was not dependent on voltage or time. The reductions in I-sK caused by propofol and thiopentone are consistent with the previously reported effects of these anaesthetics on I-Ks in the heart and support the hypothesis that the min K protein contributes to the molecular basis of the cardiac I-Ks channel.