Growth factors upregulate astrocyte [Ca²⁺]_i oscillation by increasing SERCA2b expression

Abstract

Previously, we reported upregulation of astrocyte [Ca(2+)](i) oscillation by growth factors (i.e., conversion of glutamate-induced sustained [Ca(2+)](i) increase in astrocytes cultured in a defined medium to [Ca(2+)](i) oscillation by EGF and bFGF treatment over 48 h) (Morita et al., (2003) J Neurosci 23:10944-10952). As our previous study also showed that these growth factors increase intracellular Ca(2+) stores, this study was performed to investigate the mechanism underlying loading of intracellular Ca(2+) stores in astrocytes, especially sarco-endoplasmic reticulum Ca(2+) ATPase (SERCA), as a candidate mechanism by which growth factors upregulate [Ca(2+)](i) oscillation. The results indicated that the growth factors upregulated a SERCA inhibitor-sensitive component of [Ca(2+)](i) clearance, and increased expression of the SERCA subtype, SERCA2b. Furthermore, treating the growth factor-treated astrocytes with a low concentration of SERCA inhibitor to partially inhibit SERCA reduced the level of intracellular Ca(2+) storage and reversed glutamate-induced [Ca(2+)](i) oscillations to sustained [Ca(2+)](i) increases. Thus, the upregulation of [Ca(2+)](i) oscillations was attributed to the upregulation of SERCA activities. These results indicated that these growth factors regulate the pattern of glutamate-induced astrocyte [Ca(2+)](i) increases via SERCA2b expression.

Glial Cells Physiologically Modulate Clock Neurons and Circadian Behavior in a Calcium-Dependent Manner

“…To determine whether glial Ca 2+ stores are essential for circadian rhythmicity, we examined CaP60A , the fly homolog of SERCA, an ATPase present in the ER that regulates cytosolic levels of the cation [49]. The SERCA-2b isoform is expressed in mammalian primary cultured astrocytes, and it functions in the regulation of astrocytic calcium waves and gliotransmission [24,62]. In Drosophila, a single ubiquitously-expressed SERCA isoform exists [49] with known roles in the regulation of neuronal membrane excitability [50] and ERK-mediated transcription [63].…”

Ca2+-dependent Transcriptional Control of Ca2+ Homeostasis

“…Calcium up-regulates SERCA2 expression in cardiac myocytes through the calcineurin/NFAT pathway (52,63), an effect that is blocked by induction of glycogen synthase kinase-3, a negative regulator of NFAT nuclear translocation (64). Furthermore, Ca 2ϩ oscillations regulate SERCA2 expression in astrocytes after growth factor receptor stimulation (65) and in human lens epithelial cells (66), although there is no evidence of NFAT binding to the SERCA2 promoter. In addition, MAPK-and PKC-dependent induction of Erg1 results in down-regulation of the SERCA2 gene, although, again, the effect is probably indirect because no functional Erg1-binding sites are found in the SERCA2 promoter (10,67,68).…”

The transmembrane transporter domain of glutamate transporters is a process tip localizer

“…The coverslips with the COS-7 cells or the primary cultured astrocytes were transferred to a glass-bottomed culture plates filled with HBSS42 for confocal imaging. Imaging of hippocampal organotypic slice cultures was carried out in a circulating solution containing (mM): NaCl 119; KCl 2.5; CaCl 2 4; MgCl 2 4; NaHCO 3 26.2; NaH 2 PO 4 1 and glucose 11, aerated with 95% O 2 and 5% CO 2 .…”