Depolarization of Cellular Resting Membrane Potential Promotes Neonatal Cardiomyocyte Proliferation In Vitro.
Depolarization of Cellular Resting Membrane Potential Promotes Neonatal Cardiomyocyte Proliferation In Vitro.
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DOI：
10.1007/s12195-014-0346-7
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发表时间：
2014-09-01
影响因子：
2.8
通讯作者：
Black, Lauren Deems, III
中科院分区：
文献类型：
--
作者：
Lan, Jen-Yu;Williams, Corin;Levin, Michael;Black, Lauren Deems, III
心肌细胞（CM）在出生后很快经历从增生到肥大生长的快速转变，这是用于儿科患者的工程化心脏组织的开发的主要挑战。静息膜电位（Resting membrane potential，VEP）在细胞发育过程中的分化和增殖中起重要作用。我们假设新生儿CM的去极化将刺激或维持CM在体外增殖。为了验证我们的假设，我们分离出生后第3天的新生大鼠CM，并通过向培养基中加入葡萄糖酸钾或哇巴因使其持续去极化。细胞密度和CM百分比测量表明，有丝分裂CM沿着增加，CM数量随着去极化增加约2倍。此外，去极化导致G2和S期细胞增加，表明增殖增加，如通过流式细胞术测量的。令人惊讶的是，用任何一种处理的VEGFR2的去极化导致心脏成纤维细胞增殖的抑制。当对出生后第7天的新生儿CM进行研究时，这种效应被消除，新生儿CM的增殖性较低，这表明去极化的可能机制是维持增殖的CM群体。总之，我们的研究结果表明，去极化维持出生后CM增殖，并可能是一种新的方法，以鼓励儿童患者的工程组织和心脏再生的生长。
Cardiomyocytes (CMs) undergo a rapid transition from hyperplastic to hypertrophic growth soon after birth, which is a major challenge to the development of engineered cardiac tissue for pediatric patients. Resting membrane potential (Vmem) has been shown to play an important role in cell differentiation and proliferation during development. We hypothesized that depolarization of neonatal CMs would stimulate or maintain CM proliferation in vitro. To test our hypothesis, we isolated postnatal day 3 neonatal rat CMs and subjected them to sustained depolarization via the addition of potassium gluconate or Ouabain to the culture medium. Cell density and CM percentage measurements demonstrated an increase in mitotic CMs along with a ~2 fold increase in CM numbers with depolarization. In addition, depolarization led to an increase in cells in G2 and S phase, indicating increased proliferation, as measured by flow cytometry. Surprisingly depolarization of Vmem with either treatment led to inhibition of proliferation in cardiac fibroblasts. This effect is abrogated when the study was carried out on postnatal day 7 neonatal CMs, which are less proliferative, indicating that the likely mechanism of depolarization is the maintenance of the proliferating CM population. In summary, our findings suggest that depolarization maintains postnatal CM proliferation and may be a novel approach to encourage growth of engineered tissue and cardiac regeneration in pediatric patients.
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影响因子：
5.6
作者：
CONE, CD;TONGIER, M
通讯作者：
TONGIER, M
DOI：
10.1002/wsbm.1236
发表时间：
2013-11
影响因子：
7.9
作者：
Levin, Michael
通讯作者：
Levin, Michael
影响因子：
24
作者：
Feinstein, Jeffrey A.;Benson, D. Woodrow;Martin, Gerard R.
通讯作者：
Martin, Gerard R.
影响因子：
64.8
作者：
通讯作者：
--
DOI：
10.4161/cc.8.21.9888
发表时间：
2009-11-01
期刊：
Cell cycle (Georgetown, Tex.)
影响因子：
--
作者：
Blackiston DJ;McLaughlin KA;Levin M
通讯作者：
Levin M