Effect of intravenous anesthetics on inward rectifier potassium current in rat and human ventricular myocytes

Background: Inhibition of the inward rectifying potassium current (I-K1) may cause cardiac dysrhythmias by decreasing resting membrane potential or prolonging action potential. Methods: The effects of thiopental, ketamine, and propofol on I-K1 conductance were evaluated in rat ventricular myocytes, The effect of thiopental on I-K1 conductance was also evaluated in human ventricular myocytes. Currents were recorded using the nystatin-perforated whole-cell patch-clamp technique (holding potential, -50 mV; test potentials, -140 to -40 mV). Pipette solution contained 130 mM KCl, 5 mM MgCl2, 5 mM HEPES, and 5 mM EGTA, pH 7.2. Bath solution (32 degrees C) contained 134 mM NaCl, 4 mM KCl, 1 mM MgCl2, 1 mM CaCl2, 0.3 mM CdCl2, 5 mM HEPES, and 5 mM d-glucose, pH 7.4. Drug concentrations examined encompassed the range of clinically relevant unbound plasma concentrations, Currents were normalized for cell capacitance, Conductance was calculated as current density/Delta mV from -140 to -100 mV, Analysis of variance was used to test for changes in conductance as a function of drug concentration, Results: Thiopental reduced I-K1 conductance in a concentration-dependent manner (P < 0.0001), Thiopental-induced changes in I-K1 conductance in rat ventricular myocytes were fit to an inhibitory E-max model, with a median inhibitory concentration of 10.5 mu M. The effect of thiopental on I-K1 conductance in human ventricular cells was comparable to that observed in rat ventricular myocytes, Neither ketamine nor propofol altered I-K1 conductance. Conclusions: Thiopental reduces I-K1 conductance in a concentration-dependent manner at clinically relevant concentrations in both rat and human ventricular myocytes.