Sakai F, Hiraoka M, Amaha K
Department of Anaesthesiology and Critical Care Medicine, Tokyo Medical and Dental University, Japan.
Br J Anaesth. 1996 Oct;77(4):508-16. doi: 10.1093/bja/77.4.508.
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.
我们使用全细胞膜片钳技术研究了丙泊酚和硫喷妥钠对分离的豚鼠心室肌细胞膜电位和电流的影响。电流钳制后，浓度大于0.5 μmol/L的丙泊酚缩短了平台期和动作电位时程（APD）（P<0.05）。10 μmol/L的硫喷妥钠延长了APD（P<0.05），而50 μmol/L或更高浓度则降低了平台期高度（P<0.05）和静息膜电位（RMP）（P<0.05），同时缩短了延长的APD。电压钳制时，1 μmol/L的丙泊酚将L型钙电流（ICa,L）降低至对照的88.4%（P<0.01），而不影响延迟整流钾电流（IK）；10 μmol/L的丙泊酚分别将ICa,L和IK降低至75.0%（P<0.01）和78.4%（P<0.01），对内向整流钾电流（IK1）无影响。10 μmol/L的硫喷妥钠将ICa,L降低至88.5%（P<0.01），IK降低至78.3%（P<0.05），而100 μmol/L的硫喷妥钠将ICa,L降低至82.8%（P<0.01），IK降低至27.0%（P<0.01），IK1降低至67.3%（P<0.05）。这些结果表明，高于临床相关浓度的丙泊酚主要通过抑制ICa,L缩短APD，硫喷妥钠对APD的双相作用是由IK抑制以及较高浓度时ICa,L和IK1的同时抑制引起的。丙泊酚和硫喷妥钠明显的心脏抑制作用可能至少部分归因于对膜钙电流和钾电流的不同作用。
