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

 Jee Eun Chae  ;  Hyun Soo Kim  ;  Duck Sun Ahn  ;  Wyun Kon Park 
 YONSEI MEDICAL JOURNAL, Vol.53(1) : 204-212, 2012 
Journal Title
Issue Date
Action Potentials/drug effects* ; Anesthetics, Inhalation/pharmacology* ; Animals ; Calcium Channels, L-Type/physiology ; Heart Conduction System/drug effects ; Heart Conduction System/physiology ; Heart Ventricles/drug effects ; Isoflurane/analogs & derivatives* ; Isoflurane/pharmacology ; Myocardial Contraction/drug effects* ; Myocardial Contraction/physiology ; Myocytes, Cardiac/drug effects* ; Myocytes, Cardiac/physiology ; Patch-Clamp Techniques ; Potassium Channels/physiology ; Rats ; Rats, Sprague-Dawley
Desflurane ; cardiac myocytes ; action potential ; transient outward K+ current ; rat
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.
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1. College of Medicine (의과대학) > Dept. of Physiology (생리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Medical Research Center (임상의학연구센터) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Anesthesiology and Pain Medicine (마취통증의학교실) > 1. Journal Papers
Yonsei Authors
Park, Wyun Kon(박윤곤)
Ahn, Duk Sun(안덕선) ORCID logo https://orcid.org/0000-0001-9351-6951
Chae, Jee Eun(채지은)
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