Effects of isoflurane on membrane potentials, refractory periods and membrane ionic currents in rabbit single ventricular myocytes

In order to analyze direct action of isoflurane on myocardium, we studied effects of isoflurane on membrane potentials and transmembrane ionic currents in single ventricular myocytes isolated enzymatically from rabbit hearts. Membrane potentials were recorded with a suction microelectrode technique, and an action potential was elicited by a brief intracellular stimulus. Isoflurane 3% depressed the action potential overshoot, plateau phase and duration without changing resting potential. Isoflurane decreased the refractory period of the action potential and prolonged the timeconstant (τ) of the recovery process. In corresponding voltage clamp experiments, isoflurane significantly depressed the Ca²⁺ current (I(Ca)), which generates the plateau phase. However, isoflurane had no effect on the transient outward current (I(t)), which triggers repolarization of the action potential. In rabbit ventricular cells, the time- and voltage-dependent outward K⁺ current (I(K)) was nearly absent. In conclusion, the depression of the action potential plateau by isoflurane is due to the decrease of I(Ca). Since isoflurane has no effect on I(t), the depression of the plateau phase by isoflurane may explain the shortening in the duration and the refractory period of the action potential.