title: Ionic mechanisms of desflurane on prolongation of action potential duration in rat ventricular myocytes.
abstract: OBJECTIVE
  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.
  
  
  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).
  
  
  CONCLUSIONS
  Clinically relevant concentrations of desflurane appear to prolong AP duration by suppressing I(to) in rat ventricular myocytes.
authors.affiliation: Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul , Korea.
authors.forename: Jee Eun
authors.initials: JE
authors.lastname: Chae
authors.forename: Hyun Soo
authors.initials: HS
authors.lastname: Kim
authors.forename: Duck Sun
authors.initials: DS
authors.lastname: Ahn
authors.forename: Wyun Kon
authors.initials: WK
authors.lastname: Park
mesh_terms: D000200:Action Potentials / Q000187:drug effects*; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D020746:Calcium Channels, L-Type / Q000502:physiology; D000077335:Desflurane; D006329:Heart Conduction System / Q000187:drug effects / Q000502:physiology; D006352:Heart Ventricles / Q000187:drug effects; D007530:Isoflurane / Q000031:analogs & derivatives* / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects* / Q000502:physiology; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018685:Anesthetics, Inhalation; D020746:Calcium Channels, L-Type; D015221:Potassium Channels; D000077335:Desflurane; D007530:Isoflurane