Astroglial cAMP signalling in space and time

Abstract

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. Ca²⁺ and cAMP. This enables them to communicate with neighbouring cells, such as neurons and endothelial cells of blood vessels. The dynamics of receptor-mediated Ca²⁺ 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 Ca²⁺ 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.

Keywords: Astrocytes; Receptors; Signalling; cAMP; cAMP sensors.