Structural and functional plasticity in long-term cultures of adult ventricular myocytes.
Structural and functional plasticity in long-term cultures of adult ventricular myocytes.
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DOI：
10.1016/j.yjmcc.2013.09.009
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发表时间：
2013-12
影响因子：
5
通讯作者：
Tung, Leslie
中科院分区：
文献类型：
--
作者：
Joshi-Mukherjee, Rosy;Dick, Ivy E.;Liu, Ting;O'Rourke, Brian;Yue, David T.;Tung, Leslie
关键词：
长期以来，培养的心脏细胞对于表征生物学机制和疾病发病机制具有价值。然而，这些制剂具有局限性，涉及关键性质如兴奋-收缩偶联和β-肾上腺素能刺激的不成熟。后者的进行性衰减与心力衰竭的发病机制和治疗密切相关。非常有价值的是一个长期的培养系统，它模拟伴随疾病和发育的结构和功能变化，同时允许随时进入潜在的分子事件。因此，我们在这里产生功能单层的成年豚鼠心室肌细胞（aGPVM），可以保持在长期培养数周。在基线时，这些单层表现出相当大的肌原纤维组织和肌浆网（SR）Ca 2+释放的全球Ca 2+瞬变的显着贡献。在电信号方面，这些单层支持传播的电活动，并表现出动作电位持续时间和传导速度的双相恢复。有趣的是，β-肾上腺素能刺激增加变时性，但不增加变力性，表明β-肾上腺素能信号传导的选择性维持。有趣的是，这种整体表型特征不是固定的，但可以通过培养物的慢性电刺激容易地增强。这种简单的环境线索显著增强了肌原纤维组织以及β-肾上腺素能敏感性。特别是，变时性反应增加，现在出现变力性作用，模拟心力衰竭中所见的进展逆转。因此，这些aGPVM单层培养物为阐明β-肾上腺素能信号传导及其可塑性的长期难以捉摸的特征提供了有价值的平台。
Cultured heart cells have long been valuable for characterizing biological mechanism and disease pathogenesis. However, these preparations have limitations, relating to immaturity in key properties like excitation-contraction coupling and β-adrenergic stimulation. Progressive attenuation of the latter is intimately related to pathogenesis and therapy in heart failure. Highly valuable would be a long-term culture system that emulates the structural and functional changes that accompany disease and development, while concurrently permitting ready access to underlying molecular events. Accordingly, we here produce functional monolayers of adult guinea-pig ventricular myocytes (aGPVMs) that can be maintained in long-term culture for several weeks. At baseline, these monolayers exhibit considerable myofibrillar organization and a significant contribution of sarcoplasmic reticular (SR) Ca2+ release to global Ca2+ transients. In terms of electrical signaling, these monolayers support propagated electrical activity and manifest monophasic restitution of action-potential duration and conduction velocity. Intriguingly, β-adrenergic stimulation increases chronotropy but not inotropy, indicating selective maintenance of β-adrenergic signaling. It is interesting that this overall phenotypic profile is not fixed, but can be readily enhanced by chronic electrical stimulation of cultures. This simple environmental cue significantly enhances myofibrillar organization as well as β-adrenergic sensitivity. In particular, the chronotropic response increased, and an inotropic effect now emerges, mimicking a reversal of the progression seen in heart failure. Thus, these aGPVM monolayer cultures offer a valuable platform for clarifying long elusive features of β-adrenergic signaling and its plasticity.
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影响因子：
6.1
作者：
Au, Hoi Ting Heidi;Cui, Bo;Radisic, Milica
通讯作者：
Radisic, Milica
影响因子：
--
作者：
DECKER, ML;SIMPSON, DG;DECKER, RS
通讯作者：
DECKER, RS
影响因子：
20.1
作者：
DECKER, ML;BEHNKEBARCLAY, M;DECKER, RS
通讯作者：
DECKER, RS
DOI：
10.1016/j.pbiomolbio.2012.07.012
发表时间：
2012-10
影响因子：
3.8
作者：
Blazeski A;Zhu R;Hunter DW;Weinberg SH;Boheler KR;Zambidis ET;Tung L
通讯作者：
Tung L
DOI：
10.1016/j.pbiomolbio.2012.07.013
发表时间：
2012-10
影响因子：
3.8
作者：
Blazeski A;Zhu R;Hunter DW;Weinberg SH;Zambidis ET;Tung L
通讯作者：
Tung L