Nuss H B, Houser S R
Department of Physiology, Temple University School of Medicine, Philadelphia, PA 19140.
Cardiovasc Res. 1994 Oct;28(10):1482-9. doi: 10.1093/cvr/28.10.1482.
The aim was to test the hypothesis that the prolongation of action potential duration in hypertrophied feline myocytes causes the contractions to be of long duration.
Left ventricular hypertrophy was induced by slow progressive pressure overload after banding the ascending aorta of young cats. Single myocytes were enzymatically dissociated for whole cell patch clamp studies. Cell shortenings were induced by stimulated action potentials (in current clamp mode) and by step depolarisations using voltage clamp to control the duration of depolarisation.
Action potential duration measured at 50% repolarisation (0.5 Hz) was significantly longer in hypertrophied myocytes, at 688(SEM 43) ms, n = 25, v 396(17) ms, n = 22, in control myocytes (p < 0.01). The associated contractions in hypertrophied myocytes had significantly longer durations measured at 50% relengthening [hypertrophied myocytes 609(54) ms, control myocytes 406(13) ms]. The absolute magnitude of shortening normalised to percent diastolic cell length was also significantly reduced in hypertrophied myocytes [7.8(0.8)% diastolic cell length] compared to control myocytes [12.2(0.6)% diastolic cell length] and the duration of contraction time to 50% relengthening was prolonged [406(13) ms v 609(54) ms]. When the duration of depolarisation was controlled with voltage clamp techniques, steady state contractions at +10 mV increased in magnitude in both control and hypertrophied myocytes as the duration of depolarization was lengthened. At all durations tested (100-1000 ms), contractions were significantly longer in duration in hypertrophied myocytes. Changing the duration of depolarisation had no significant effect on the duration of contraction in control myocytes. In hypertrophied myocytes, however, prolongation of depolarisation (500-1000 ms) significantly prolonged the contraction. Steady state contractions initiated from -70 mV (sodium current activated) were larger in both control and hypertrophied myocytes than contractions elicited from -40 mV (sodium current inactivated), and the effect of depolarisation duration on contractile duration was the same.
Changes in sarcolemmal properties which produce a lengthening of the action potential duration in hypertrophy are not primarily responsible for the prolongation of contractile duration. However, there is a portion of contraction which becomes sensitive to the duration of depolarisation in hypertrophied myocytes.
旨在验证肥厚型猫心肌细胞动作电位时程延长会导致收缩时程延长这一假说。
通过结扎幼猫升主动脉，缓慢渐进性压力超负荷诱导左心室肥厚。酶解分离单个心肌细胞用于全细胞膜片钳研究。通过刺激动作电位（电流钳模式）和使用电压钳进行阶跃去极化以控制去极化持续时间来诱导细胞缩短。
肥厚型心肌细胞在复极化50%时（0.5 Hz）测得的动作电位时程显著更长，为688（标准误43）毫秒，n = 25，而对照心肌细胞为396（17）毫秒，n = 22（p < 0.01）。肥厚型心肌细胞相关收缩在再拉长50%时测得的时程显著更长[肥厚型心肌细胞609（54）毫秒，对照心肌细胞406（13）毫秒]。与对照心肌细胞[舒张期细胞长度的12.2（0.6）%]相比，肥厚型心肌细胞中以舒张期细胞长度百分比标准化的缩短绝对幅度也显著降低[舒张期细胞长度的7.8（0.8）%]，且收缩至再拉长50%的时间延长[406（13）毫秒对609（54）毫秒]。当用电压钳技术控制去极化持续时间时，在对照和肥厚型心肌细胞中，随着去极化持续时间延长，在+10 mV时的稳态收缩幅度均增加。在所有测试持续时间（100 - 1000毫秒）下，肥厚型心肌细胞的收缩时程均显著更长。改变去极化持续时间对对照心肌细胞的收缩时程无显著影响。然而，在肥厚型心肌细胞中，去极化延长（500 - 1000毫秒）显著延长了收缩。从 - 70 mV（钠电流激活）起始的稳态收缩在对照和肥厚型心肌细胞中均大于从 - 40 mV（钠电流失活）引发的收缩，且去极化持续时间对收缩持续时间的影响相同。
肥厚时导致动作电位时程延长的肌膜特性变化并非收缩时程延长的主要原因。然而，肥厚型心肌细胞中存在一部分收缩对去极化持续时间变得敏感。
