Electrophysiologic mechanism underlying action potential prolongation by sevoflurane in rat ventricular myocytes.
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.
Chae
Jee Eun
JE
Anesthesia and Pain Research Institute, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
Ahn
Duck Sun
DS
Kim
Myung Hee
MH
Lynch
Carl
C
Park
Wyun Kon
WK
D015761:4-Aminopyridine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects*; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects; D002469:Cell Separation; D004594:Electrophysiology; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D008738:Methyl Ethers / Q000494:pharmacology*; D032383:Myocytes, Cardiac / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D024661:Potassium Channels, Inwardly Rectifying / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077149:Sevoflurane
D018685:Anesthetics, Inhalation; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D008738:Methyl Ethers; D024661:Potassium Channels, Inwardly Rectifying; D000077149:Sevoflurane; D015761:4-Aminopyridine