Characterisation of Development and Electrophysiological Mechanisms Underlying Rhythmicity of the Avian Lymph Heart.
Characterisation of Development and Electrophysiological Mechanisms Underlying Rhythmicity of the Avian Lymph Heart.
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DOI：
10.1371/journal.pone.0166428
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Patel K
中科院分区：
文献类型：
--
作者：
Jaffer S;Valasek P;Luke G;Batarfi M;Whalley BJ;Patel K
尽管在组织工程方面取得了重大进展，如使用支架、生物反应器和多能干细胞，但有效的用于治疗目的的心脏组织工程在很大程度上仍然是一个棘手的挑战。为了利用这些进展，一种新的方法可能是揭开组织发育的生理机制，这些组织表现出节律性收缩，但不是起源于心脏谱系。禽类淋巴心脏的生理学已经引起了相当大的关注，这是一种起源于骨骼肌的离散器官，但它表现出通常只在心脏中存在的起搏器特性。一个功能正常的淋巴心脏对于禽类在卵子中的生存和生长是必不可少的。淋巴心脏的组织学性质类似于骨骼肌，尽管在发育过程中还没有进行分子和生物电学特征来评估促成淋巴心脏收缩节律性的机制。更好地了解这些过程可能会为这一领域尚未得到满足的重大临床需求的治疗节律收缩组织工程方法提供可利用的见解。在这里，我们使用分子和电生理学的方法，描述淋巴心脏的分子发育，以了解这种骨骼肌如何在卵细胞发育的离散阶段变得完全功能。我们的结果表明，淋巴心脏并不像大多数骨骼肌那样遵循正常的肌肉发生过渡程序，而是通过前体扩张、对肌肉发生的承诺和功能分化的并行程序而发展，这为其快速发展提供了机制解释。细胞外电生理场电位记录显示，卡巴胆碱处理后，电诱发的心脏局部场电位的峰间波幅显著降低，这种作用可被阿托品完全逆转。此外，硝苯地平和环匹亚硝酸均显著降低局部场电位的峰间波幅。淋巴心脏的光学记录显示，器官的节律性可以被HCN通道阻滞剂ZD7288阻断；这种效果还与峰间局部场电位幅度的显著降低有关。此外，我们还发现HCN通道的异构体在禽类淋巴心脏中表达。这些结果表明，胆碱能信号和L钙通道在兴奋和收缩偶联中起重要作用，而HCN通道在维持淋巴性心律中起重要作用。
Despite significant advances in tissue engineering such as the use of scaffolds, bioreactors and pluripotent stem cells, effective cardiac tissue engineering for therapeutic purposes has remained a largely intractable challenge. For this area to capitalise on such advances, a novel approach may be to unravel the physiological mechanisms underlying the development of tissues that exhibit rhythmic contraction yet do not originate from the cardiac lineage. Considerable attention has been focused on the physiology of the avian lymph heart, a discrete organ with skeletal muscle origins yet which displays pacemaker properties normally only found in the heart. A functional lymph heart is essential for avian survival and growth in ovo. The histological nature of the lymph heart is similar to skeletal muscle although molecular and bioelectrical characterisation during development to assess mechanisms that contribute towards lymph heart contractile rhythmicity have not been undertaken. A better understanding of these processes may provide exploitable insights for therapeutic rhythmically contractile tissue engineering approaches in this area of significant unmet clinical need. Here, using molecular and electrophysiological approaches, we describe the molecular development of the lymph heart to understand how this skeletal muscle becomes fully functional during discrete in ovo stages of development. Our results show that the lymph heart does not follow the normal transitional programme of myogenesis as documented in most skeletal muscle, but instead develops through a concurrent programme of precursor expansion, commitment to myogenesis and functional differentiation which offers a mechanistic explanation for its rapid development. Extracellular electrophysiological field potential recordings revealed that the peak-to-peak amplitude of electrically evoked local field potentials elicited from isolated lymph heart were significantly reduced by treatment with carbachol; an effect that could be fully reversed by atropine. Moreover, nifedipine and cyclopiazonic acid both significantly reduced peak-to-peak local field potential amplitude. Optical recordings of lymph heart showed that the organ’s rhythmicity can be blocked by the HCN channel blocker, ZD7288; an effect also associated with a significant reduction in peak-to-peak local field potential amplitude. Additionally, we also show that isoforms of HCN channels are expressed in avian lymph heart. These results demonstrate that cholinergic signalling and L-type Ca2+ channels are important in excitation and contraction coupling, while HCN channels contribute to maintenance of lymph heart rhythmicity.
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影响因子：
7.3
作者：
BOSMITH, RE;BRIGGS, I;STURGESS, NC
通讯作者：
STURGESS, NC
DOI：
10.1679/aohc.46.115
发表时间：
1983-01-01
期刊：
ARCHIVUM HISTOLOGICUM JAPONICUM
影响因子：
--
作者：
SATOH, Y;NITATORI, T
通讯作者：
NITATORI, T
DOI：
10.1126/science.1171643
发表时间：
2009-06-26
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Discher DE;Mooney DJ;Zandstra PW
通讯作者：
Zandstra PW
影响因子：
9.2
作者：
Amthor, H;Christ, B;Patel, K
通讯作者：
Patel, K
影响因子：
--
作者：
DELCASTILLO, J;SANCHEZ, V
通讯作者：
SANCHEZ, V