Modulation of cardiac inward rectifier K+ current by halothane and isoflurane

The cellular mechanisms that underlie general anesthetic actions on the inw ard rectifier K+ current (IKir), a determinant of the resting potential in myocardium, are not fully understood. Using the whole-cell patch clamp tech nique, therefore, we investigated the effects of halothane and isoflurane o n IKir in guinea pig ventricular myocytes. At membrane potentials negative to the equilibrium potential for potassium both anesthetics decreased ampli tude Of the shady-state inward IKir in a concentration- and voltage-depende nt manner. The slope conductance was reduced, but the activation kinetics o f the inward current were not altered. At potentials positive to the equili brium potential for potassium, the outward current was increased by both an esthetics, which also caused small depolarizing shifts in the activation cu rve. With high internal magnesium concentration, the outward current increa se by isoflurane was abolished, and the inward current block by halothane w as attenuated. Spermine prevented the effects of both anesthetics on IKir a t all membrane potentials tested. The results show voltage-dependent modula tion of cardiac IKir channel by volatile anesthetics. Distinct modification of anesthetic effects by inward rectification gating agents, magnesium and spermine, suggests anesthetic interactions with the IKir channel protein I mplications: Differential modulation of myocardial inward rectifier potassi um current by volatile anesthetics under normal and altered rectification m ay contribute to the mechanism of dysrhythmic actions by these anesthetics.