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Electrophysiologic mechanism underlying action potential prolongation by sevoflurane in rat ventricular myocytes.
Anesthesiology. 2007 Jul; 107(1):67-74.A

Abstract

BACKGROUND

Despite prolongation of the QTc interval in humans during sevoflurane anesthesia, little is known about the mechanisms that underlie these actions. In rat ventricular myocytes, the effect of sevoflurane on action potential duration and underlying electrophysiologic mechanisms were investigated.

METHODS

The action potential was measured by using a current clamp technique. The transient outward K current was recorded during depolarizing steps from -80 mV, followed by brief depolarization to -40 mV and then depolarization up to +60 mV. The voltage dependence of steady state inactivation was determined by using a standard double-pulse protocol. The sustained outward current was obtained by addition of 5 mm 4-aminopyridine. The inward rectifier K current was recorded from a holding potential of -40 mV before their membrane potential was changed from -130 to 0 mV. Sevoflurane actions on L-type Ca current were also obtained.

RESULTS

Sevoflurane prolonged action potential duration, whereas the amplitude and resting membrane potential remained unchanged. The peak transient outward K current at +60 mV was reduced by 18 +/- 2% (P < 0.05) and 24 +/- 2% (P < 0.05) by 0.35 and 0.7 mm sevoflurane, respectively. Sevoflurane had no effect on the sustained outward current. Whereas 0.7 mm sevoflurane did not shift the steady state inactivation curve, it accelerated the current inactivation (P < 0.05). The inward rectifier K current at -130 mV was little altered by 0.7 mm sevoflurane. L-type Ca current was reduced by 28 +/- 3% (P < 0.05) and 33 +/- 1% (P < 0.05) by 0.35 and 0.7 mm sevoflurane, respectively.

CONCLUSIONS

Action potential prolongation by clinically relevant concentrations of sevoflurane is due to the suppression of transient outward K current in rat ventricular myocytes.

Authors+Show Affiliations

Chae JE
Anesthesia and Pain Research Institute, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
Ahn DS
No affiliation info available
Kim MH
No affiliation info available
Lynch C
No affiliation info available
Park WK
No affiliation info available

MeSH

4-AminopyridineAction PotentialsAnesthetics, InhalationAnimalsCalcium Channel BlockersCalcium Channels, L-TypeCell SeparationElectrophysiologyHeart VentriclesIn Vitro TechniquesMembrane PotentialsMethyl EthersMyocytes, CardiacPatch-Clamp TechniquesPotassium Channels, Inwardly RectifyingRatsRats, Sprague-DawleySevoflurane

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17585217

Citation

Chae, Jee Eun, et al. "Electrophysiologic Mechanism Underlying Action Potential Prolongation By Sevoflurane in Rat Ventricular Myocytes." Anesthesiology, vol. 107, no. 1, 2007, pp. 67-74.
Chae JE, Ahn DS, Kim MH, et al. Electrophysiologic mechanism underlying action potential prolongation by sevoflurane in rat ventricular myocytes. Anesthesiology. 2007;107(1):67-74.
Chae, J. E., Ahn, D. S., Kim, M. H., Lynch, C., & Park, W. K. (2007). Electrophysiologic mechanism underlying action potential prolongation by sevoflurane in rat ventricular myocytes. Anesthesiology, 107(1), 67-74.
Chae JE, et al. Electrophysiologic Mechanism Underlying Action Potential Prolongation By Sevoflurane in Rat Ventricular Myocytes. Anesthesiology. 2007;107(1):67-74. PubMed PMID: 17585217.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Electrophysiologic mechanism underlying action potential prolongation by sevoflurane in rat ventricular myocytes. AU - Chae,Jee Eun, AU - Ahn,Duck Sun, AU - Kim,Myung Hee, AU - Lynch,Carl,3rd AU - Park,Wyun Kon, PY - 2007/6/23/pubmed PY - 2007/8/31/medline PY - 2007/6/23/entrez SP - 67 EP - 74 JF - Anesthesiology JO - Anesthesiology VL - 107 IS - 1 N2 - BACKGROUND: Despite prolongation of the QTc interval in humans during sevoflurane anesthesia, little is known about the mechanisms that underlie these actions. In rat ventricular myocytes, the effect of sevoflurane on action potential duration and underlying electrophysiologic mechanisms were investigated. METHODS: The action potential was measured by using a current clamp technique. The transient outward K current was recorded during depolarizing steps from -80 mV, followed by brief depolarization to -40 mV and then depolarization up to +60 mV. The voltage dependence of steady state inactivation was determined by using a standard double-pulse protocol. The sustained outward current was obtained by addition of 5 mm 4-aminopyridine. The inward rectifier K current was recorded from a holding potential of -40 mV before their membrane potential was changed from -130 to 0 mV. Sevoflurane actions on L-type Ca current were also obtained. RESULTS: Sevoflurane prolonged action potential duration, whereas the amplitude and resting membrane potential remained unchanged. The peak transient outward K current at +60 mV was reduced by 18 +/- 2% (P < 0.05) and 24 +/- 2% (P < 0.05) by 0.35 and 0.7 mm sevoflurane, respectively. Sevoflurane had no effect on the sustained outward current. Whereas 0.7 mm sevoflurane did not shift the steady state inactivation curve, it accelerated the current inactivation (P < 0.05). The inward rectifier K current at -130 mV was little altered by 0.7 mm sevoflurane. L-type Ca current was reduced by 28 +/- 3% (P < 0.05) and 33 +/- 1% (P < 0.05) by 0.35 and 0.7 mm sevoflurane, respectively. CONCLUSIONS: Action potential prolongation by clinically relevant concentrations of sevoflurane is due to the suppression of transient outward K current in rat ventricular myocytes. SN - 0003-3022 UR - https://www.unboundmedicine.com/medline/citation/17585217/Electrophysiologic_mechanism_underlying_action_potential_prolongation_by_sevoflurane_in_rat_ventricular_myocytes_ DB - PRIME DP - Unbound Medicine ER -