Stage-dependent changes in membrane currents in rats with monocrotaline-induced right ventricular hypertrophy
Stage-dependent changes in membrane currents in rats with monocrotaline-induced right ventricular hypertrophy
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DOI：
10.1152/ajpheart.1997.272.6.h2833
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发表时间：
1997-06-01
影响因子：
4.8
通讯作者：
Toyama, J
中科院分区：
文献类型：
--
作者：
Lee, JK;Kodama, I;Toyama, J
在野百合碱（MCT）诱导的肺动脉高压大鼠心室肌细胞上观察了动作电位构型、4-氨基吡啶敏感性瞬时外向电流（I-to）和L型钙电流（I-Ca）的顺序变化及其与肥厚的关系。皮下注射MCT后14天和28天，右心室（RV）与左心室加室间隔的组织重量比分别增加了29.7%和77.2%。MCT大鼠RV细胞动作电位时程（APD）进行性增加，第14天和第28天分别延长73.2%和92.2%。在粘土14上，MCT大鼠RV细胞中的I-to电流密度（32.5 +/- 4.5 pA/pF，n = 13）显著大于对照组（26.8 +/- 4.5 pA/pF，n = 8; P < 0.05）。然而，在第28天，MCT大鼠的It密度（15.3 +/- 4.6 pA/pF，n = 9）显著低于对照组（27.3 +/- 4.2 pA/pF，n = 10; P < 0.05）。MCT和对照组大鼠的I-to稳态激活和失活的电压依赖性无差异。第14天MCT大鼠的I-Ca密度（15.7 +/- 2.6 pA/pF，n = 10）显著大于对照组（10.0 ± 2.3 pA/pF，n = 10; P < 0.05），但MCT组间I-to密度无显著性差异（8.3 +/- 3.7 pA/pF，n = 10）和对照组（11.6 +/- 3.0 pA/pF，n = 10）。这些结果表明，哺乳动物的心脏肥大可能会导致阶段依赖性的变化，在I-to和I-Ca，心室肌细胞密度。心肌肥厚早期APD延长可能主要是由于I-Ca浓度增加所致，而心肌肥厚晚期APD延长可能是由于I-to浓度降低所致。
Sequential changes in action potential configuration, 4-aminopyridine-sensitive transient outward current (I-to), and L-type calcium current (I-Ca) in association with hypertrophy were investigated in ventricular myocytes from rats with monocrotaline (MCT)-induced pulmonary hypertension. The tissue weight ratio of right ventricle (RV) to left ventricle plus septum 14 and 28 days after a subcutaneous injection of MCT increased by 29.7 and 77.2%, respectively. Action potential duration (APD) of RV cells from MCT rats increased progressively, prolonged by 73.2 and 92.2% on days 14 and 28, respectively. The current density of I-to in RV cells from MCT rats on clay 14 (32.5 +/- 4.5 pA/pF, n = 13) was significantly larger than in controls (26.8 +/- 4.5 pA/pF, n = 8; P < 0.05). On day 28, however, It, density in MCT rats (15.3 +/- 4.6 pA/pF, n = 9) was significantly less than in controls (27.3 +/- 4.2 pA/pF, n = 10; P < 0.05). There were no differences in the voltage dependence of steady-state activation and inactivation of I-to between MCT and control rats. I-Ca density in MCT rats on day 14 (15.7 +/- 2.6 pA/pF, n = 10) was significantly larger than in controls (10.0 +/- 2.3 pA/pF, n = 10; P < 0.05), but there was no significant difference in I-to density between MCT rats (8.3 +/- 3.7 pA/pF, n = 10) and controls (11.6 +/- 3.0 pA/pF, n = 10) on day 28. These findings suggest that hypertrophy of mammalian hearts may cause stage-dependent changes in I-to and I-Ca, density of ventricular myocytes. The APD prolongation in the early stage of hypertrophy may be caused mainly by an increase in I-Ca density, whereas the APD prolongation in the late stage may be ascribed to a reduction in I-to density.