Ionic Mechanisms of Desflurane on Prolongation of Action Potential Duration in Rat Ventricular Myocytes.
10.3349/ymj.2012.53.1.204
- Author:
Jee Eun CHAE
1
;
Hyun Soo KIM
;
Duck Sun AHN
;
Wyun Kon PARK
Author Information
1. Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul, Korea.
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
Desflurane;
cardiac myocytes;
action potential;
transient outward K+ current;
rat
- MeSH:
Action Potentials/*drug effects;
Anesthetics, Inhalation/*pharmacology;
Animals;
Calcium Channels, L-Type/physiology;
Heart Conduction System/drug effects/physiology;
Heart Ventricles/drug effects;
Isoflurane/*analogs & derivatives/pharmacology;
Myocardial Contraction/*drug effects/physiology;
Myocytes, Cardiac/*drug effects/physiology;
Patch-Clamp Techniques;
Potassium Channels/physiology;
Rats;
Rats, Sprague-Dawley
- From:Yonsei Medical Journal
2012;53(1):204-212
- CountryRepublic of Korea
- Language:English
-
Abstract:
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 Ito in rat ventricular myocytes.
