Modulation of cardiac inward rectifier K(+)current by halothane and isoflurane.
The cellular mechanisms that underlie general anesthetic actions on the inward rectifier K(+) current (IKir), a determinant of the resting potential in myocardium, are not fully understood. Using the whole-cell patch clamp technique, therefore, we investigated the effects of halothane and isoflurane on IKir in guinea pig ventricular myocytes. At membrane potentials negative to the equilibrium potential for potassium both anesthetics decreased amplitude of the steady-state inward IKir in a concentration- and voltage-dependent manner. The slope conductance was reduced, but the activation kinetics of the inward current were not altered. At potentials positive to the equilibrium potential for potassium, the outward current was increased by both anesthetics, which also caused small depolarizing shifts in the activation curve. With high internal magnesium concentration, the outward current increase by isoflurane was abolished, and the inward current block by halothane was attenuated. Spermine prevented the effects of both anesthetics on IKir at all membrane potentials tested. The results show voltage-dependent modulation of cardiac IKir channel by volatile anesthetics. Distinct modification of anesthetic effects by inward rectification gating agents, magnesium and spermine, suggests anesthetic interactions with the IKir channel protein.


CONCLUSIONS
Differential modulation of myocardial inward rectifier potassium current by volatile anesthetics under normal and altered rectification may contribute to the mechanism of dysrhythmic actions by these anesthetics.
Stadnicka
A
A
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA. astadnic@mcw.edu
Bosnjak
Z J
ZJ
Kampine
J P
JP
Kwok
W M
WM
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006221:Halothane / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D007530:Isoflurane / Q000494:pharmacology*; D008274:Magnesium / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects*; D013096:Spermine / Q000494:pharmacology
D018685:Anesthetics, Inhalation; D015221:Potassium Channels; D013096:Spermine; D007530:Isoflurane; D008274:Magnesium; D006221:Halothane