Comparative actions of propofol and thiopentone on cell membranes of isolated guineapig ventricular myocytes.
We have examined the effects of propofol and thiopentone on membrane potentials and currents of isolated guineapig ventricular myocytes using the whole-cell patch-clamp technique. After current clamping, propofol at concentrations greater than 0.5 mumol litre-1 shortened the plateau and action potential duration (APD) (P < 0.05). Thiopentone 10 mumol litre-1 prolonged APD (P < 0.05), whereas concentrations of 50 mumol litre-1 or higher decreased plateau height (P < 0.05) and resting membrane potential (RMP) (P < 0.05) with abbreviation of the prolonged APD. With voltage clamping, propofol 1 mumol litre-1 decreased the L-type Ca2+ current (ICa,L) to 88.4% of control (P < 0.01) without affecting the delayed rectifier K+ current (IK) and propofol 10 mumol litre-1 decreased ICa,L and IK to 75.0% (P < 0.01) and 78.4% (P < 0.01), respectively, with no effect on the inward rectifier K+ current (IK1). Thiopentone 10 mumol litre-1 decreased ICa,L to 88.5% (P < 0.01) and IK to 78.3% (P < 0.05), while thiopentone 100 mumol litre-1 depressed ICa,L to 82.8% (P < 0.01), IK to 27.0% (P < 0.01) and IK1 to 67.3% (P < 0.05). These results indicated that propofol, at concentrations greater than those that are clinically relevant, shortened APD mainly by suppression of ICa,L, and the biphasic effects on APD by thiopentone were caused by depression of IK, and concomitant suppression of ICa,L and IK1 at higher concentrations. The distinct cardiodepressant effects of propofol and thiopentone may be, at least in part, attributed to different actions on membrane Ca2+ and K+ currents.
Sakai
F
F
Department of Anaesthesiology and Critical Care Medicine, Tokyo Medical and Dental University, Japan.
Hiraoka
M
M
Amaha
K
K
D000200:Action Potentials / Q000187:drug effects; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D018929:Cell Culture Techniques; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006352:Heart Ventricles / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D015742:Propofol / Q000494:pharmacology*; D013874:Thiopental / Q000494:pharmacology*
D018686:Anesthetics, Intravenous; D013874:Thiopental; D011188:Potassium; D002118:Calcium; D015742:Propofol