异丙酚对人心房肌细胞ATP敏感性钾电流的影响

Effects of propofol on ATP sensitive K^+ currents in human atrial myocytes

目的 探讨不同浓度的异丙酚对人离体心房肌细胞 ATP 敏感性钾电流(I_KATP)的影响及电生理改变。方法取房缺或室缺修补术病人的右心耳组织，置于100%氧饱和无钙心肌细胞冷保护液中，并在30min 内送至实验室。将标本剪成1mm^3小块，用二步酶解法分离出单一心房肌细胞。用膜片钳全细胞记录方法，观察不同浓度异丙酚(0.003、0.03和0.3mmol·L^(-1))对心房肌单一细胞I_KATP的影响。结果 在电极内液含 ATP(0.3mmol·L^(-1))条件下，记录到一束外向 K~＋电流。该电流可被K_ATP 通道特异阻滞药格列苯脲(10μmol·L^(-1))抑制，表明此电流为 I_KATP。异丙酚使 I_KATP 外流增加，且浓度与电流激活率呈线性回归(r^2=0.9999，P<0.05)。结论 异丙酚通过浓度依赖方式激活心房肌细胞 I_(KATP)，对人心房肌具有抑制作用。

Objective To investigate the effects of different doses of propofor on ATP-sensitive K^+currents(I_KATP)in human atrial myocytes and the underlying mechsnism.Methods A small piece of myocardiumwas obtained from right atrium in patients undergoing atrial septal defect or ventricular septal defect surgery.Themyocardium specimen was placed in cold Ca^(2+)-free cardioplegic solution aerated with 100% oxygen.Themyocardium specimen was cut into small chunks(1 mm^3).Atrial myocytes were isolated by enzymatic dissociationtechnique.The effects of propofol on I_KATP in atrial myocytes were studied using the whole-cell configuration ofpatch-clamp technique.Results The outward currents were recorded with a pipitte solution containing 0.3mmol·L^(-1) ATP.The currents were inhibited by glibendamide 10 μmol·L^(-1),a specific K_ATP channel inhibitor,suggesting that the outward currents were I_KATP.I_KATP aws activited by propofol in a dose-dependent manner.Conclusion Propefol can activate the I_KATP in human myocytes in a concentration-dependent manner and themechanism of its myocardial depressant action may be partly explained.