硫喷妥钠对人心房肌细胞瞬间外向钾电流的影响

Effects of thiopental sodium on transient outward K * currents in human atrial myocytes

目的 观察硫喷妥钠对人心肌细胞瞬间外向钾通道电流(Itol)的影响,探讨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(T1组)、100μmol/L(T2组)、300μmol/L(T3组)]对细胞膜瞬间外向钾电流的影响。结果 T1组硫喷妥钠在+30～+60 mV有抑制Itol的趋势,其中,在+50 mv和+60 mv有明显抑制作用(n=21,P<0.05);T2组和T3组硫喷妥钠分别在测试电位+30～+60mv(n=19)和+20-+60 mV(n=17)时,对Itol有明显抑制作用(P<0.05);并且在膜电位去极化至+60 mV时,三组浓度(30μmol/L、100 μmol/L、300μmol/L)的硫喷妥钠对电流的抑制率分别为10.7±3.3、21.3±3.8和(49.3±4.8)％,不同浓度效应间差异具有显著性(P<0.05),且抑制程度与浓度呈正相关(r=0.943,P<0.05)。电流-电压曲线基本形态无显著变化。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Itol有明显而直接的抑制作用,且具有浓度依赖性,提示这种改变与硫喷妥钠的心肌抑制作用中的负性变时性作用有关。

Objective To investigate the effects of thiopental sodium on transient outward K + currents (Itol) in human atrial myocytes using whole-cell patch clamp technique.Methods Human atrial myocytes were prepared by digestion with collagenase followed by gradual recalcification to 0.6 mmol · L-1 . Different concentrations of thiopental sodium were added to the cell suspensions (end-concentration of thiopental =30, 100 and 300μmol · L-1 ). Transient outward K+ currents (Itol) in atrial myocytes were measured and recorded before and after addition of thiopental using whole-cell patch clamp technique. Results Holding potential ( Vh) was set at - 80 mV and testing potential (Vt) at + 50 and + 60 mV, thiopental caused significant decrease in Itol densities in a dose-dependent fashion. For example at + 60 mV (Vt) Itol density was significantly reduced by thiopental from 7.7 ±0.6 pA/pF (before thiopental) to 6.9 ?0.5 pA/pF (30 μmol·L-1 ), 6.1 ±0.4 pA/PF (100 μmol· L-1) and 3.8±0.5 pA/pF (300μmol·L-1) ( P < 0.05). Conclusion Clinical concentrations of thiopental exert direct inhibitory effects on Itol in human atrial myocytes, which may explain the underlying mechanism of myocardial depression induced by thiopental anesthesia.