Department of Pathology and Cell Regulation, Kyoto Prefectural University of Medicine, Graduate School of Medical Science , Kyoto, 602-8566, Japan.
Department of Pathology and Cell Regulation, Kyoto Prefectural University of Medicine, Graduate School of Medical Science , Kyoto, 602-8566, Japan ; Department of Pathology, National Cerebral and Cardiovascular Center, Suita, Osaka 565-8565, Japan.
Acta Histochem Cytochem. 2014 May 1;47(2):59-65. doi: 10.1267/ahc.14014. Epub 2014 Apr 25.
Intracellular Ca(2+) ([Ca(2+)]i) dynamics in isolated myocytes differ between the atria and ventricles due to the distinct t-tubular distributions. Although cellular aspects of ventricular [Ca(2+)]i dynamics in the heart have been extensively studied, little is known about those of atrial myocytes in situ. Here we visualized precise [Ca(2+)]i dynamics of atrial myocytes in Langendorff-perfused rat hearts by rapid-scanning confocal microscopy. Of 16 fluo-4-loaded hearts imaged during pacing up to 4-Hz, five hearts showed spatially uniform Ca(2+) transients on systole among individual cells, whereas no discernible [Ca(2+)]i elevation developed during diastole. In contrast, the remaining hearts showed non-uniform [Ca(2+)]i dynamics within and among the cells especially under high-frequency (4 Hz) excitation, where subcellular cluster-like [Ca(2+)]i rises or wave-like [Ca(2+)]i propagation occurred on excitation. Such [Ca(2+)]i inhomogeneity was more pronounced at high-frequency pacing, showing beat-to-beat Ca(2+) transient alternans. Despite such non-uniform dynamics, cessation of burst pacing of the atria was not followed by emergence of spontaneous Ca(2+) waves, indicating minor Ca(2+)-releasing potentials of the sarcoplasmic reticulum (SR). In summary, rat atria display a propensity to show non-uniform [Ca(2+)]i dynamics on systole due to impaired Ca(2+)-release from the SR and paucity of t-tubules. Our results provide an important basis for understanding atrial pathophysiology.
细胞内钙离子([Ca^2+]i)动力学在分离的心肌细胞中因横管分布的不同而在心房和心室之间存在差异。尽管心脏心室[Ca^2+]i动力学的细胞方面已经得到了广泛的研究,但对于原位心房心肌细胞的了解甚少。在这里,我们通过快速扫描共聚焦显微镜可视化了 Langendorff 灌注大鼠心脏中心房心肌细胞的精确[Ca^2+]i动力学。在起搏至 4Hz 的过程中对 16 个加载 fluo-4 的心脏进行成像,在五个心脏中,个体细胞在收缩期间表现出空间均匀的 Ca^2+ 瞬变,而在舒张期间没有可辨别的[Ca^2+]i 升高。相比之下,在剩余的心脏中,尤其是在高频(4Hz)刺激下,细胞内和细胞间表现出非均匀的[Ca^2+]i 动力学,其中亚细胞簇状[Ca^2+]i 升高或波状[Ca^2+]i 传播发生在兴奋时。这种[Ca^2+]i 非均匀性在高频起搏时更为明显,表现出跳动间 Ca^2+ 瞬变交替。尽管存在这种非均匀动力学,但心房的爆发起搏停止后不会出现自发的 Ca^2+ 波,表明肌浆网(SR)的 Ca^2+ 释放电位较小。总之,由于 SR 从 Ca^2+ 释放受损和横管稀少,大鼠心房在收缩时表现出倾向于表现出非均匀的[Ca^2+]i 动力学。我们的结果为理解心房病理生理学提供了重要基础。