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

Abstract

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 transcribedin 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 –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 I_sK. The estimated IC₅₀ value for the block of I_sK by propofol was 250 μΜ and by thiopentone was 56 μΜ. 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.