Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan, USA.
Physiol Rep. 2023 Aug;11(15):e15779. doi: 10.14814/phy2.15779.
Remodeling of cardiac t-tubules in normal and pathophysiological conditions is an important process contributing to the functional performance of the heart. While it is well documented that deterioration of t-tubule network associated with various pathological conditions can be reversed under certain conditions, the mechanistic understanding of the recovery process is essentially lacking. Accordingly, in this study we investigated some aspects of the recovery of t-tubules after experimentally-induced detubulation. T-tubules of isolated mouse ventricular myocytes were first sealed using osmotic shock approach, and their recovery under various experimental conditions was then characterized using electrophysiologic and imaging techniques. The data show that t-tubule recovery is a strongly temperature-dependent process involving reopening of previously collapsed t-tubular segments. T-tubule recovery is slowed by (1) metabolic inhibition of cells, (2) reducing influx of extracellular Ca as well as by (3) both stabilization and disruption of microtubules. Overall, the data show that t-tubule recovery is a highly dynamic process involving several central intracellular structures and processes and lay the basis for more detailed investigations in this area.
心脏 T 小管在正常和病理生理条件下的重塑是促进心脏功能表现的重要过程。虽然有充分的文献记载表明,与各种病理状况相关的 T 小管网络的恶化在某些条件下可以逆转,但对恢复过程的机制理解基本上还缺乏。因此,在这项研究中,我们研究了实验诱导去小管化后 T 小管恢复的一些方面。首先使用渗透休克方法封闭分离的小鼠心室肌细胞中的 T 小管,然后使用电生理和成像技术来描述它们在各种实验条件下的恢复情况。数据表明,T 小管恢复是一个强烈依赖于温度的过程,涉及先前塌陷的 T 管状段的重新开放。T 小管恢复受到以下因素的抑制:(1)细胞代谢抑制;(2)减少细胞外 Ca 流入;以及(3)微管的稳定和破坏。总体而言,这些数据表明 T 小管恢复是一个涉及几个核心细胞内结构和过程的高度动态过程,并为该领域的更详细研究奠定了基础。