硫喷妥钠对人心肌细胞内向整流钾通道电流的影响

Effects of thiopentone of inward rectifier K^+ current in human atrial myocytes

目的 通过观察静脉麻醉药硫喷妥钠对人心肌细胞内向整流钾通道电流(Ik1)的影响,评价其对心肌抑制作用中可能的电生理改变作用。方法 采用急性分离的人心房肌细胞,应用膜片钳全细胞技术记录不同浓度的硫喷妥钠(30μmol/L、100μmol,L、300μmol/L)对细胞膜内向整流钾电流的影响。结果30μmol/L硫喷妥钠轻度抑制Ik1外向成分(+10 mV-+40mv,n=14个细胞,P<0.05),100μmol/L和300μmol/L硫喷妥钠分别同时抑制了Ik1内向(分别在测试电位-70mv--120mV)和外向(测试电位分别为0mV-+40 mV和-10 mv-+40 mv)成分(n=14个细胞,P<0.05)。在测试电位为+20 mV时,三组浓度(30、100、300μmol/L)的硫喷妥钠对电流的抑制率分别为:15.2％±2.1％、42.2％±5.0％和75.4％±5.7％,抑制程度与浓度呈正相关(r=0.968,P<0.05)。给予100μmol/L硫喷妥钠后,静息膜电位(RMP)由给药前的(-69.0±1.0)mV分别降为(-63.2±1.3)mV(n=12个细胞,P<0.05)和(-61.7±0.9)mV(n=9个细胞,P<0.05)。结论临床相关及其高于临床浓度的硫喷妥钠对人心房肌细胞内向整流钾电流有直接的和部分可逆性抑制作用,抑制效应具有浓度依赖性,提示这种改变与硫喷妥钠的心肌抑制作用,尤其是负性变时性作用有关。

Objective To investigate the effects of thiopentone on inward rectifier K+ current (IK1 ) in human cardiac myocytes. Methods The effects of thiopentone on acutely isolated human atrial myocytes were studied using the whole-cell patch clamp technique. Different concentrations of thiopentone (30 μmol/L, 100 μmol/L,300μmol/L) were added and then IK1 and rest membrane potential (RMP) were measured. Results Lower concentration of thiopentone (30μmol/L) only slightly inhibited the outward component of IK1 ; whereas the higher concentrations of thiopentone (100 μmol/L and 300μmol/L) significantly decreased both inward and outward components of IK1 . In addition the RMP was reduced from ( - 69±1.0) mV to ( - 63.2 ±1.3) mV (by 100 μmol/L) and ( - 61.7 ±0.9) mV (by 300 μmol/L) respectively. Conclusion Clinical and higher concentration of thiopentone exert marked, direct and partially reversible inhibitory effects on IK1 and the inhibition is concentration-dependent. These changes may explain the depressant action of thiopentone (especially negative chronotropism).