不同年龄大鼠心肌细胞瞬时外向钾电流的变化

发布时间：2018-09-18 20:56

【摘要】：本文旨在研究心肌细胞瞬时外向钾电流(transient outward potassium current,Ito)的随龄变化及其药物反应性改变。Sprague Dawley大鼠28只,分为青年组(3~5月龄)、成年组(13~15月龄)和老年组(22~24月龄)。酶法分离心室肌细胞,应用全细胞膜片钳技术记录各组Ito。并于细胞外液分别加入1.0μmol/L异丙肾上腺素和2.0mmol/L4-氨基吡啶干预,观察Ito的变化。结果显示,与青年组和成年组相比,老年组Ito电流密度显著增加。门控动力学研究显示,老年组Ito电流稳态激活曲线左移,通道关闭态失活速率明显降低,稳态失活后恢复速率加快,而稳态失活过程无明显变化。老年组Ito对选择性抑制剂4-氨基吡啶的反应性与青年组和成年组相似,但老年组Ito对β受体激动剂异丙肾上腺素的反应性却明显弱于青年组和成年组,各组电流密度分别增加55.9%、127.5%和125.8%。上述结果提示,随着大鼠年龄的增加,心肌细胞Ito电流密度显著升高,与通道门控的激活、关闭态失活和失活后恢复机制改变有关,且老年鼠Ito对异丙肾上腺素的反应性降低。
[Abstract]:The purpose of this study was to study the changes of transient outward potassium current (transient outward potassium current,Ito) in cardiomyocytes with age and their drug reactivity. 28 Sprague Dawley rats were divided into three groups: young group (3 ~ 5 months old), adult group (13 ~ 15 months old) and elderly group (22 ~ 24 months old). Ventricular myocytes were isolated by enzymatic method and Ito. was recorded by whole-cell patch clamp technique. 1. 0 渭 mol/L isoproterenol and 2. 0 mmol / L 4-aminopyridine were added to the extracellular fluid to observe the changes of Ito. The results showed that the current density of Ito in the elderly group was significantly higher than that in the young group and adult group. The gated dynamics study showed that the steady-state activation curve of Ito in the elderly group shifted to the left, the deactivation rate of the closed channel decreased significantly, the recovery rate increased after steady-state inactivation, but the steady-state inactivation process did not change significantly. The reactivity of Ito to selective inhibitor 4-aminopyridine in elderly group was similar to that in young group and adult group, but the reactivity of Ito to 尾 -agonist isoproterenol was significantly weaker in elderly group than that in young group and adult group. The current density of each group increased by 55.9% and 125.8%, respectively. These results suggest that Ito current density in cardiac myocytes increases significantly with the increase of age, which is related to channel gated activation, closed inactivation and changes of recovery mechanism after inactivation, and the reactivity of Ito to isoproterenol in aged rats is decreased.
【作者单位】：解放军总医院老年心血管病研究所;
【基金】：supported by the National Natural Science Foundation of China(No.30770901)
【分类号】：R331

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