Purpose: Despite the fact that desflurane prolongs the QTC interval in humans, little is known about the mechanisms that underlie these actions. We investigated the effects of desflurane on action potential (AP) duration and underlying electrophysiological mechanisms in rat ventricular myocytes.
Materials and methods: Rat ventricular myocytes were enzymatically isolated and studied at room temperature. AP was measured using a current clamp technique. The effects of 6% (0.78 mM) and 12% (1.23 mM) desflurane on transient outward K⁺ current (I(to)), sustained outward current (I(sus)), inward rectifier K⁺ current (I(KI)), and L-type Ca²⁺ current were determined using a whole cell voltage clamp.
Results: Desflurane prolonged AP duration, while the amplitude and resting membrane potential remained unchanged. Desflurane at 0.78 mM and 1.23 mM significantly reduced the peak I(to) by 20 ± 8% and 32 ± 7%, respectively, at +60 mV. Desflurane (1.23 mM) shifted the steady-state inactivation curve in a hyperpolarizing direction and accelerated inactivation of the current. While desflurane (1.23 mM) had no effects on I(sus) and I(KI), it reduced the L-type Ca²⁺ current by 40 ± 6% (p<0.05).
Conclusion: Clinically relevant concentrations of desflurane appear to prolong AP duration by suppressing I(to) in rat ventricular myocytes.