Horvat Anemari, Vardjan Nina
Laboratory of Neuroendocrinology-Molecular Cell Physiology, Institute of Pathophysiology, Faculty of Medicine, University of Ljubljana, Zaloška 4, 1000 Ljubljana, Slovenia; Laboratory of Cell Engineering, Celica Biomedical, Tehnološki Park 24, 1000 Ljubljana, Slovenia.
Laboratory of Neuroendocrinology-Molecular Cell Physiology, Institute of Pathophysiology, Faculty of Medicine, University of Ljubljana, Zaloška 4, 1000 Ljubljana, Slovenia; Laboratory of Cell Engineering, Celica Biomedical, Tehnološki Park 24, 1000 Ljubljana, Slovenia.
Neurosci Lett. 2019 Jan 10;689:5-10. doi: 10.1016/j.neulet.2018.06.025. Epub 2018 Jun 14.
To maintain a high level of specificity and normal cell function, the cyclic adenosine monophosphate (cAMP) pathway is tightly regulated in space and time. Recent advances in cAMP reporter technology have provided insights into spatio-temporal characteristics of cAMP signalling in individual living cells, including astrocytes. Astrocytes are glial cells in the central nervous system with many homeostatic functions. In contrast to neurons, astrocytes are electrically silent, but, in response to extracellular stimuli through activation of surface receptors, they can increase intracellular levels of secondary messengers, e.g. Ca and cAMP. This enables them to communicate with neighbouring cells, such as neurons and endothelial cells of blood vessels. The dynamics of receptor-mediated Ca signalling in astrocytes has been extensively studied in the past in contrast to cAMP signalling. Here, we present the first insights into the temporal dynamics of cAMP signalling in living astrocytes, which revealed that cAMP signals in astrocytes exhibit tonic dynamics and are slower than Ca signals with phasic dynamics. We debate on the heterogeneity of basal cAMP levels in astrocytes and how hypotonicity-induced astrocyte swelling affects temporal dynamics of cAMP signalling. Understanding the spatio-temporal characteristics of cAMP signalling in astrocytes is of extreme importance because cAMP governs many important cellular processes and any malfunctions may lead to pathology.
为维持高度的特异性和正常细胞功能，环磷酸腺苷（cAMP）信号通路在空间和时间上受到严格调控。cAMP报告基因技术的最新进展为深入了解包括星形胶质细胞在内的单个活细胞中cAMP信号的时空特征提供了线索。星形胶质细胞是中枢神经系统中的神经胶质细胞，具有多种稳态功能。与神经元不同，星形胶质细胞电沉默，但通过激活表面受体对细胞外刺激作出反应时，它们可以增加细胞内第二信使的水平，如Ca和cAMP。这使它们能够与邻近细胞，如神经元和血管内皮细胞进行通讯。过去，与cAMP信号传导相比，星形胶质细胞中受体介导的Ca信号动力学已得到广泛研究。在此，我们首次深入了解了活星形胶质细胞中cAMP信号的时间动态，结果表明星形胶质细胞中的cAMP信号表现出持续性动态，且比具有相位性动态的Ca信号慢。我们讨论了星形胶质细胞中基础cAMP水平的异质性以及低渗诱导的星形胶质细胞肿胀如何影响cAMP信号的时间动态。了解星形胶质细胞中cAMP信号的时空特征至关重要，因为cAMP控制着许多重要的细胞过程，任何功能失调都可能导致病理状态。
