The effects of isoflurane on the cardiac slowly activating delayed-rectifier potassium channel in Guinea pig ventricular myocytes. Anesth Analg 2003 May;96(5):1308-1315
Date
04/23/2003Pubmed ID
12707124DOI
10.1213/01.ANE.0000057604.56578.77Scopus ID
2-s2.0-0037406182 (requires institutional sign-in at Scopus site) 41 CitationsAbstract
UNLABELLED: The slowly activating delayed-rectifier potassium current, IKs, is a major outward current responsible for the repolarization of the cardiac action potential (AP). Dysfunction of this channel can lead to AP prolongation, resulting in the long QT syndrome. We hypothesized that anesthetic-induced AP prolongation is caused by inhibition of IKs, in addition to the inhibition of IKr (rapidly activating delayed-rectifier potassium channel current), a condition often found in drug-induced AP prolongation. The whole-cell patch clamp technique was used to study the effects of isoflurane on IKs and IKr recorded from guinea pig single ventricular myocytes. The effect of protein kinase C on IKs inhibition by isoflurane was also investigated. Isoflurane inhibited IKs in a concentration- and temperature-dependent manner. The inhibitory effects of isoflurane at clinically relevant concentrations of 0.3 and 0.6 mM were greater at 22 degrees C than at 36 degrees C. Voltage-dependent activation of IKs was not affected at these concentrations. IKs deactivation kinetics were accelerated by isoflurane at 22 degrees C but not at 36 degrees C. Isoflurane inhibition of IKs was significantly greater than that of IKr. Protein kinase C activation enhanced IKs but did not suppress the inhibitory effect of isoflurane. Our results suggest that IKs inhibition is one of the mechanisms underlying anesthetic-induced AP and QT prolongation. Because most of the ion channel studies on anesthetic effects are conducted at room temperature, the temperature-dependent effect on IKs confirms the importance of anesthetic experiments conducted at physiological temperature.
IMPLICATIONS: The effects of a volatile anesthetic, isoflurane, were determined on a cardiac potassium channel current, IKs, a major ionic component underlying the cardiac action potential. The result shows that IKs is significantly inhibited by isoflurane. This may contribute to anesthetic-induced changes in the electrocardiogram, particularly the prolongation of the QT interval.
Author List
Suzuki A, Bosnjak ZJ, Kwok WMAuthor
Wai-Meng Kwok PhD Professor in the Anesthesiology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Action PotentialsAlgorithms
Anesthetics, Inhalation
Animals
Dose-Response Relationship, Drug
Guinea Pigs
Heart Ventricles
In Vitro Techniques
Isoflurane
Kinetics
Membrane Potentials
Myocardium
Patch-Clamp Techniques
Potassium Channel Blockers
Potassium Channels
Potassium Channels, Voltage-Gated
Protein Kinase C
Temperature
Tetradecanoylphorbol Acetate
