Morphological profile determines the frequency of spontaneous calcium events in astrocytic processes

Astrocytes express a complex repertoire of intracellular Ca2+ transients (events) that represent a major form of signaling within individual cells and in astrocytic syncytium. These events have different spatiotemporal profiles, which are modulated by neuronal activity. Spontaneous Ca2+ events appea...

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Veröffentlicht in:	Glia Jg. 67; H. 2; S. 246 - 262
Hauptverfasser:	Wu, Yu‐Wei, Gordleeva, Susan, Tang, Xiaofang, Shih, Pei‐Yu, Dembitskaya, Yulia, Semyanov, Alexey
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	Hoboken, USA John Wiley & Sons, Inc 01.02.2019 Wiley Subscription Services, Inc
Schlagworte:	Animals astrocyte Astrocytes Astrocytes - drug effects Astrocytes - metabolism Astrocytes - ultrastructure Benzylamines - pharmacology Calcium Calcium (extracellular) Calcium (intracellular) Calcium - metabolism calcium channel Calcium channels Calcium channels (voltage-gated) Calcium imaging Calcium ions Calcium Signaling - drug effects Calcium Signaling - physiology Calcium signalling Calcium-Calmodulin-Dependent Protein Kinase Type 2 - genetics Calcium-Calmodulin-Dependent Protein Kinase Type 2 - metabolism Cell culture Cells, Cultured Channels Coculture Techniques Coding Depolarization Embryo, Mammalian Excitatory Amino Acid Antagonists - pharmacology Fluctuations GABA Antagonists - pharmacology GCaMP Genetic code Hippocampus Hippocampus - cytology Inositol 1,4,5-trisphosphate receptors Intracellular signalling IP3 receptors Mathematical models microdomain Mitochondria - drug effects Mitochondria - metabolism Models, Biological Morphology Neurons - drug effects Neurons - physiology Phosphinic Acids - pharmacology process Rats Rats, Wistar Receptors Sodium Channel Blockers - pharmacology Territory Tetrodotoxin - pharmacology Transfection GCaMP calcium channel IP3 receptors process microdomain astrocyte calcium imaging
ISSN:	0894-1491, 1098-1136, 1098-1136
Online-Zugang:	Volltext
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Zusammenfassung:	Astrocytes express a complex repertoire of intracellular Ca2+ transients (events) that represent a major form of signaling within individual cells and in astrocytic syncytium. These events have different spatiotemporal profiles, which are modulated by neuronal activity. Spontaneous Ca2+ events appear more frequently in distal astrocytic processes and independently from each other. However, little is known about the mechanisms underlying such subcellular distribution of the Ca2+ events. Here, we identify the initiation points of the Ca2+ events within the territory of single astrocytes expressing genetically encoded Ca2+ indicator GCaMP2 in culture or in hippocampal slices. We found that most of the Ca2+ events start in an optimal range of thin distal processes. Our mathematical model demonstrated that a high surface‐to‐volume of the thin processes leads to increased amplitude of baseline Ca2+ fluctuations caused by a stochastic opening of Ca2+ channels in the plasma membrane. Suprathreshold fluctuations trigger Ca2+‐induced Ca2+ release from the Ca2+ stores by activating inositol 1,4,5‐trisphosphate (IP3) receptors. In agreement with the model prediction, the spontaneous Ca2+ events frequency depended on the extracellular Ca2+ concentration. Astrocytic depolarization by high extracellular K+ increased the frequency of the Ca2+ events through activation of voltage‐gated Ca2+ channels in cultured astrocytes. Our results suggest that the morphological profile of the astrocytic processes is responsible for tuning of the Ca2+ events frequency. Therefore, structural plasticity of astrocytic processes can be directly translated into changes in astrocytic Ca2+ signaling. This may be important for both physiological and pathological astrocyte remodeling. Majority of spontaneous Ca2+ events start in thin astrocytic processes. Higher surface‐to‐volume ratio of the process is responsible for larger intracellular Ca2+ fluctuations. Larger intracellular Ca2+ fluctuations trigger Ca2+‐dependent Ca2+ release.
Bibliographie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	0894-1491 1098-1136 1098-1136
DOI:	10.1002/glia.23537