新生大鼠心肌细胞短暂外向钾电流下降与心肌肥大的相关性研究

在某些心力衰竭患者中常观察到心肌细胞短暂外向钾电流 (Ito)下降和动作电位时程 (APD)延长 ,笔者主要探讨Ito下降与心肌肥大的关系及内在机制。用Ito阻断剂 ,4 氨基吡啶 (4 AP) ,处理新生大鼠心室肌细胞 ,观察作为心肌肥大指标的细胞膜电容和3 H 亮氨酸 (3 H Leu)掺入量 ,同时测Ito振幅和APD。结果 :Ito振幅下降近 5 0 %(1 5 0 .3± 1 8.6pA ,n =7vs 74 .0± 1 1 .5pA ,n =1 1 ,P <0 .0 5 )。APD50 (5 0 %复极 )显著的延长 (75 .8± 1 4 .1ms,n =7vs2 0 1 .7± 2 3.5ms,n =1 1 ,P <0 .0 5 )。膜电容和3 H Leu掺入量分别增加 4 7%和 31 % (P均 <0 .0 5 )。L 型钙通道阻断剂维拉帕米 ,能抑制 4 AP诱导的APD延长以及膜电容和3 H 亮氨酸掺入量的增加。环孢素A(CsA)也可抑制 4 AP诱导的膜电容和3 H Leu掺入量的增加 ,但对APD影响不明显。结论 :Ito下降通过延长APD ,致细胞内钙增加 ,激活钙调神经磷酸酶反应途径 ,可能引起心肌肥大

Hypertrophy Associated With Reduction of Ito in Neonatal Rat Ventricular Myocytes

Decreased transient outward potassium current(Ito) and prolonged action potential duration(APD) are commonly observed in some of heart diseases. The purpose of this study is to investigate the relations between reduction of Ito and myocardial hypertrophy and explore its mechanism. Treatment of cultured neonatal rat ventricular myocytes with 4 Aminopyridine, a blocker of cardiac Ito, induced hypertrophy as indicated by measurements of the cell membrane capacitance and 3H Leucine up take. At the same time,amplitude of Ito and APD were also measured. Results:The amplitude of Ito was reduced by about 50% (150.3±18.6 pA,n=7 vs 74.0±11.5 pA, n=11,P<0.05). APD 50 (50% repolarization) was prolonged significantly (75.8±14.1ms, n=7 vs 201.7±23.5 ms, n=11,P<0.05). The membrane capacitance and the uptake of 3H Leu were increased by about 47%(P<0.05) and 31%( P<0.05).The hypertrophy was prevented by blocking Ca 2+ entry with Verapamil and blocking calcineurin with Cyclosporine A. Conclusion: Reduction of Ito plays an important role in hypertrophy by the increment of intracellular Ca 2+ and activity of calcineurin reaction pathway.