Differential effects of cytochalasin D and 2,3 butanedione monoxime on isometric twitch force and transmembrane action potential in isolated ventricular muscle: Implications for optical measurements of cardiac repolarization
Differential effects of cytochalasin D and 2,3 butanedione monoxime on isometric twitch force and transmembrane action potential in isolated ventricular muscle: Implications for optical measurements of cardiac repolarization
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DOI：
10.1111/j.1540-8167.1998.tb00110.x
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发表时间：
1998-12-01
影响因子：
2.7
通讯作者：
Zipes, DP
中科院分区：
文献类型：
--
作者：
Biermann, M;Rubart, M;Zipes, DP
细胞松弛素D诱导的心脏收缩衰竭。简介：2，3-丁二酮单肟（BDM）在光学记录心肌膜电压变化过程中被广泛用于抑制收缩，尽管它能显著增强心肌动作电位。方法和结果：我们比较了BDM和F-肌动蛋白破坏剂细胞松弛素D（cyto D）对灌流台氏液的离体犬右心室小梁等长收缩力和跨膜动作电位的影响（2 mmol/L CaCl 2，37 ℃）和0.5 Hz刺激，10 mmol/L BDM和80 μ mol/L cyto D在将峰值等长收缩力分别降低至10% +/- 3%（n = 6;平均值+/- SEM）和8% +/- 1%（n = 8）方面同样有效。两种药物均未显著改变静息张力。10 mmol/L BDM使动作电位90%复极化时程（APD（90））从198 +/- 7 msec缩短至146 +/- 9 msec（P < 0.001），而80 μ mol/L cyto D对APD（90）及其他动作电位参数无明显影响。BDM对等长收缩力峰值和APD的影响在洗脱15分钟后完全可逆，而cyto D组收缩力继续降低（13% +/- 3%）和动作电位特征在用不含细胞色素D的台氏液灌注60分钟后未显示出与对照值相比的显著变化。我们的结论是，cyto D应被视为一种替代的兴奋-收缩解偶联剂的心脏复极的光学标测研究。
Cytochalasin D Induced Cardiac Contraction Failure. Introduction: 2,3-Butanedione monoxime (BDM) has been widely used to inhibit contraction during optical recordings of cardiac membrane voltage changes, even though it markedly abbreviates cardiac action potentials.Methods and Results: We compared the effects of BDM and of the F-actin disrupter cytochalasin D (cyto D) on isometric twitch force and transmembrane action potentials in isolated canine right ventricular trabeculae superfused with Tyrode's solution (2 mmol/L CaCl2, 37 degrees C) and stimulated at 0.5 Hz, BDM at 10 mmol/L and cyto D at 80 mu mol/L were equally effective in reducing peak isometric force to 10% +/- 3% (n = 6; mean +/- SEM) and 8% +/- 1% (n = 8), respectively. Neither agent significantly altered resting tension. While 10 mmol/L BDM markedly shortened the action potential duration at 90% repolarization (APD(90)) from 198 +/- 7 msec to 146 +/- 9 msec (P < 0.001), 80 mu mol/L cyto D had no significant effects on APD(90) or on any other action potential parameter. The effects of BDM on peak isometric force and APD were completely reversible after 15 minutes of washout, whereas in the cyto D group contractile force continued to be reduced (13% +/- 3%) and action potential characteristics did not show significant changes from control values after a 60-minute period of superfusion with cyto D-free Tyrode's solution.Conclusion: We conclude that cyto D should be considered an alternative excitation-contraction uncoupler for optical mapping studies of cardiac repolarization.