Barbiturate anesthetics depress the resting K+ conductance of myocardium.
The intravenous anesthestic thiopental has been previously shown to increase the incidence of ventricular arrhythmias, particularly when combined with epinephrine and halothane. Recent work based on microelectrode and tension measurements has indicated that thiopental may diminish membrane K+ permeability. Utilizing the whole-cell patch-clamp technique, we investigated the effect of thiopental on the current associated with the resting membrane conductance, the anomalous or inward rectifying K+ current (IK1). External application of 30 microM thiopental to frog atrial myocytes resulted in a 56 +/- 2% (mean +/- S.E.M.; n = 12 cells) reduction in the magnitude of IK1 elicited by a hyperpolarization to -110 mV. The outward current component through IK1 channels, evoked by depolarizing voltages above the resting potential, was decreased to same extent. The effect of thiopental on IK1 was concentration-dependent and the time courses of onset and recovery were rapid (tau = 10-14 sec). Ramp command potentials from -120 to +60 mV at a rate of 20 mV/sec revealed that 30 microM thiopental also depressed the delayed outward K+ current by 25 +/- 4% (n = 4). Examination of other barbiturates revealed that the potency in the suppression of IK1 was related to the octanol/water partition coefficient, suggesting a lipophilic site of action. Utilizing guinea pig ventricular myocytes, we observed a similar level of IK1 depression with thiopental, however the rates of onset and recovery were considerably slower than with frog atrial myocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
Pancrazio
J J
JJ
Department of Anesthesiology, University of Virginia Health Sciences Center, Charlottesville.
Frazer
M J
MJ
Lynch
C
C
D000200:Action Potentials / Q000187:drug effects; D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D001001:Anura; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D003198:Computer Simulation; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism*; D013874:Thiopental / Q000494:pharmacology*
D000777:Anesthetics; D013874:Thiopental; D011188:Potassium; D002118:Calcium