Ionic mechanisms of desflurane on prolongation of action potential duration in rat ventricular myocytes

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.