EFFECT OF INTRAVENOUS ANESTHETICS ON INWARD RECTIFIER POTASSIUM CURRENT IN RAT AND HUMAN VENTRICULAR MYOCYTES

Background: Inhibition of the inward rectifying potassium current (I-K 1) may cause cardiac dysrhythmias by decreasing resting membrane poten tial or prolonging action potential. Methods: The effects of thiopenta l, ketamine, and propofol on I-K1 conductance were evaluated in rat ve ntricular myocytes, The effect of thiopental on I-K1 conductance was a lso evaluated in human ventricular myocytes. Currents were recorded us ing 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. B ath solution (32 degrees C) contained 134 mM NaCl, 4 mM KCl, 1 mM MgCl 2, 1 mM CaCl2, 0.3 mM CdCl2, 5 mM HEPES, and 5 mM d-glucose, pH 7.4. D rug concentrations examined encompassed the range of clinically releva nt unbound plasma concentrations, Currents were normalized for cell ca pacitance, 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 < 0.00 01), Thiopental-induced changes in I-K1 conductance in rat ventricular myocytes were fit to an inhibitory E-max model, with a median inhibit ory concentration of 10.5 mu M. The effect of thiopental on I-K1 condu ctance in human ventricular cells was comparable to that observed in r at ventricular myocytes, Neither ketamine nor propofol altered I-K1 co nductance. Conclusions: Thiopental reduces I-K1 conductance in a conce ntration-dependent manner at clinically relevant concentrations in bot h rat and human ventricular myocytes.