Effects of sevoflurane on inward rectifier K+ current in guinea pig ventricular cardiomyocytes.
The effects of sevoflurane on the inward rectifier potassium current (IKIR) were examined in guinea pig ventricular cardiomyocytes using the whole cell patch-clamp methodology. Sevoflurane had a unique dual effect on the steady-state current amplitude, producing a reversible, concentration- and voltage-dependent block of the inward current at potentials negative to the potassium equilibrium potential (EK) but enhancing the outward current positive to EK. Accordingly, the steady-state conductance negative to EK was reduced by sevoflurane, but conductance positive to EK was increased. The chord conductance-voltage relationship showed depolarizing shifts at 0.7, 1.3, and 1.6 mM sevoflurane. When the myocytes were dialyzed with 10 mM Mg2+, but not with 1.0 mM Mg2+, sevoflurane further slowed current activation kinetics. With 10 mM intracellular Mg2+, the outward current enhancement by sevoflurane and the associated shifts in half-activation potential were abolished. Polyamines abolished all effects of sevoflurane on IKIR. With the use of the Woodhull model for voltage-dependent block, we determined the sevoflurane interaction site with the inward rectifier potassium channel to be at an electrical distance of 0.2 from the extracellular side.
Stadnicka
A
A
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee 53226, USA.
Bosnjak
Z J
ZJ
Kampine
J P
JP
Kwok
W M
WM
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004987:Ethers / Q000494:pharmacology*; D006168:Guinea Pigs; D006321:Heart / Q000502:physiology*; D006352:Heart Ventricles; D007700:Kinetics; D008274:Magnesium / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D008738:Methyl Ethers; D008954:Models, Biological; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying; D012044:Regression Analysis; D000077149:Sevoflurane; D013095:Spermidine / Q000494:pharmacology; D013096:Spermine / Q000494:pharmacology
D018685:Anesthetics, Inhalation; D004987:Ethers; D008738:Methyl Ethers; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D013096:Spermine; D000077149:Sevoflurane; D008274:Magnesium; D013095:Spermidine