Comparison of the T-tubule system in adult rat ventricular and atrial myocytes, and its role in excitation-contraction coupling and inotropic stimulation

Comparison of the T-tubule system in adult rat ventricular and atrial myocytes, and its role in excitation-contraction coupling and inotropic stimulation
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DOI:
10.1016/j.ceca.2009.10.001
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发表时间:
2010-03-01
期刊:
影响因子:
4
通讯作者:
Bootman, Martin D.
Bootman, Martin D.
中科院分区:
生物学2区
文献类型:
--
作者:
Smyrnias, Ioannis;Mair, Waltraud;Bootman, Martin D.

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肌膜("T-管")的狭窄、管状、向内突出是成年哺乳动物心室肌细胞的既定特征,其使它们能够产生全细胞Ca2+瞬变并产生协调收缩。T-小管的损失可发生在衰老期间和病理条件下,导致心脏兴奋-收缩偶联改变。与成年心室细胞相反,心房肌细胞在发育的任何阶段通常不表达广泛的T-小管系统,因此依赖于其外周周围的Ca2+通道来诱导Ca2+信号传导和兴奋-收缩偶联。因此,在成年心室和心房肌细胞的收缩Ca 2+信号的特性是时间和空间上不同的。然而,尽管心房肌细胞不具有与成年心室细胞相同的规则间隔的曲T-小管结构,但已表明一部分成年心房细胞具有更基本的小管系统。我们研究了这些心房小管的结构和功能,并探讨了它们对电起搏肌细胞中Ca2+信号传导的启动和恢复的影响。心房的反应进行了比较,在成年心室细胞,有完整的T-小管,或已被化学去管。我们发现,管状结构存在于一个显着的少数成年心房肌细胞,不像在成年心室细胞的T-小管。在这些细胞中,它们存在,心房小管显着改变的开始,幅度,均匀性和恢复的Ca2+瞬变。成年心房肌细胞Ca2+信号的性质不同于成年心室肌细胞,无论是完整的还是去微管的。因此,在去微管的成年心室肌细胞中的兴奋-收缩偶联不接近心房信号传导,即使在这两种情况下,Ca2+信号在细胞的外周中启动。此外,对内皮素-1的变力性反应完全依赖于成年心室肌细胞的T-小管,但不依赖于心房细胞。我们的数据表明,心房细胞中的T-小管赋予显着的功能特性,但这些管状膜的损失并不影响Ca2+信号作为显着的心室肌细胞中的去管化。(C)2009爱思唯尔有限公司保留所有权利。
Narrow, tubular, inward projections of the sarcolemma ('T-tubules') are an established feature of adult mammalian ventricular myocytes that enables them to generate the whole-cell Ca2+ transients and produce coordinated contraction. Loss of T-tubules can occur during ageing and under pathological conditions, leading to altered cardiac excitation-contraction coupling. In contrast to adult ventricular cells, atrial myocytes do not generally express an extensive T-tubule system at any stage of development, and therefore rely on Ca2+ channels around their periphery for the induction of Ca2+ signalling and excitation-contraction coupling. Consequently, the characteristics of systolic Ca2+ signals in adult ventricular and atrial myocytes are temporally and spatially distinct. However, although atrial myocytes do not have the same regularly spaced convoluted T-tubule structures as adult ventricular cells, it has been suggested that a proportion of adult atrial cells have a more rudimentary tubule system. We examined the structure and function of these atrial tubules, and explored their impact on the initiation and recovery of Ca2+ signalling in electrically paced myocytes. The atrial responses were compared to those in adult ventricular cells that had intact T-tubules, or that had been chemically detubulated. We found that tubular structures were present in a significant minority of adult atrial myocytes, and were unlike the T-tubules in adult ventricular cells. In those cells where they were present, the atrial tubules significantly altered the on-set, amplitude, homogeneity and recovery of Ca2+ transients. The properties of adult atrial myocyte Ca2+ signals were different from those in adult ventricular cells, whether intact or detubulated. Excitation-contraction coupling in detubulated adult ventricular myocytes, therefore, does not approximate to atrial signalling, even though Ca2+ signals are initiated in the periphery of the cells in both of these situations. Furthermore, inotropic responses to endothelin-1 were entirely dependent on T-tubules in adult ventricular myocytes, but not in atrial cells. Our data reveal that that the T-tubules in atrial cells impart significant functional properties, but loss of these tubular membranes does not affect Ca2+ signalling as dramatically as detubulation in ventricular myocytes. (C) 2009 Elsevier Ltd. All rights reserved.