scholarly journals Calcium Sensors STIM1 and STIM2 Regulate Different Calcium Functions in Cultured Hippocampal Neurons

2021 ◽  
Vol 12 ◽  
Author(s):  
Liliya Kushnireva ◽  
Eduard Korkotian ◽  
Menahem Segal
Keyword(s):  
Dendritic Spines ◽  
Hippocampal Neurons ◽  
Calcium Entry ◽  
Calcium Stores ◽  
Plastic Properties ◽  
Calcium Sensors ◽  
Central Neurons ◽  
Transient Rise ◽  
Store Operated Calcium Entry ◽  
Adult Neuron

There are growing indications for the involvement of calcium stores in the plastic properties of neurons and particularly in dendritic spines of central neurons. The store-operated calcium entry (SOCE) channels are assumed to be activated by the calcium sensor stromal interaction molecule (STIM)which leads to activation of its associated Orai channel. There are two STIM species, and the differential role of the two in SOCE is not entirely clear. In the present study, we were able to distinguish between transfected STIM1, which is more mobile primarily in young neurons, and STIM2 which is less mobile and more prominent in older neurons in culture. STIM1 mobility is associated with spontaneous calcium sparks, local transient rise in cytosolic [Ca2+]i, and in the formation and elongation of dendritic filopodia/spines. In contrast, STIM2 is associated with older neurons, where it is mobile and moves into dendritic spines primarily when cytosolic [Ca2+]i levels are reduced, apparently to activate resident Orai channels. These results highlight a role for STIM1 in the regulation of [Ca2+]i fluctuations associated with the formation of dendritic spines or filopodia in the developing neuron, whereas STIM2 is associated with the maintenance of calcium entry into stores in the adult neuron.

Store-operated calcium entry compensates fast ER calcium loss in resting hippocampal neurons

Cell Calcium ◽  
2015 ◽  
Vol 58 (2) ◽  
pp. 147-159 ◽  
Author(s):  
Samira Samtleben ◽  
Britta Wachter ◽  
Robert Blum
Keyword(s):  
Hippocampal Neurons ◽  
Calcium Entry ◽  
Store Operated Calcium Entry ◽  
Calcium Loss ◽  
Er Calcium

scholarly journals Dexamethasone stimulates store-operated calcium entry and protein degradation in cultured L6 myotubes through a phospholipase A2-dependent mechanism

2010 ◽  
Vol 298 (5) ◽  
pp. C1127-C1139 ◽  
Author(s):  
Kiyoshi Itagaki ◽  
Michael Menconi ◽  
Bozena Antoniu ◽  
Qin Zhang ◽  
Patricia Gonnella ◽  
...  
Keyword(s):  
Calcium Channel ◽  
Protein Degradation ◽  
Intracellular Calcium ◽  
Muscle Wasting ◽  
Muscle Protein ◽  
Calcium Entry ◽  
Calcium Stores ◽  
Fluorescence Measurements ◽  
Store Operated Calcium Entry

Muscle wasting in various catabolic conditions is at least in part regulated by glucocorticoids. Increased calcium levels have been reported in atrophying muscle. Mechanisms regulating calcium homeostasis in muscle wasting, in particular the role of glucocorticoids, are poorly understood. Here we tested the hypothesis that glucocorticoids increase intracellular calcium concentrations in skeletal muscle and stimulate store-operated calcium entry (SOCE) and that these effects of glucocorticoids may at least in part be responsible for glucocorticoid-induced protein degradation. Treatment of cultured myotubes with dexamethasone, a frequently used in vitro model of muscle wasting, resulted in increased intracellular calcium concentrations determined by fura-2 AM fluorescence measurements. When SOCE was measured by using calcium “add-back” to muscle cells after depletion of intracellular calcium stores, results showed that SOCE was increased 15–25% by dexamethasone and that this response to dexamethasone was inhibited by the store-operated calcium channel blocker BTP2. Dexamethasone treatment stimulated the activity of calcium-independent phospholipase A2(iPLA2), and dexamethasone-induced increase in SOCE was reduced by the iPLA2inhibitor bromoenol lactone (BEL). In additional experiments, treatment of myotubes with the store-operated calcium channel inhibitor gadolinium ion or BEL reduced dexamethasone-induced increase in protein degradation. Taken together, the results suggest that glucocorticoids increase calcium concentrations in myocytes and stimulate iPLA2-dependent SOCE and that glucocorticoid-induced muscle protein degradation may at least in part be regulated by increased iPLA2activity, SOCE, and cellular calcium levels.

scholarly journals Calcium stores regulate excitability in cultured rat hippocampal neurons

2018 ◽  
Vol 120 (5) ◽  
pp. 2694-2705 ◽  
Author(s):  
Menahem Segal
Keyword(s):  
Action Potential ◽  
Hippocampal Neurons ◽  
Extracellular Calcium ◽  
Calcium Stores ◽  
Sk Channels ◽  
Central Neurons ◽  
Action Potential Threshold ◽  
Potential Threshold ◽  
Small Conductance ◽  
Cultured Hippocampal Neurons

Extracellular calcium ions support synaptic activity but also reduce excitability of central neurons. In the present study, the effect of calcium on excitability was explored in cultured hippocampal neurons. CaCl2 injected by pressure in the vicinity of a neuron that is bathed only in MgCl2 as the main divalent cation caused a depolarizing shift in action potential threshold and a reduction in excitability. This effect was not seen if the intracellular milieu consisted of Cs+ instead of K-gluconate as the main cation or when it contained ruthenium red, which blocks release of calcium from stores. The suppression of excitability by calcium was mimicked by caffeine, and calcium store antagonists cyclopiazonic acid or thapsigargin blocked this action. Neurons taken from synaptopodin-knockout mice show significantly reduced efficacy of calcium modulation of action potential threshold. Likewise, in Orai1 knockdown cells, calcium is less effective in modulating excitability of neurons. Activation of small-conductance K (SK) channels increased action potential threshold akin to that produced by calcium ions, whereas blockade of SK channels but not big K channels reduced the threshold for action potential discharge. These results indicate that calcium released from stores may suppress excitability of central neurons. NEW & NOTEWORTHY Extracellular calcium reduces excitability of cultured hippocampal neurons. This effect is mediated by calcium-gated potassium currents, possibly small-conductance K channels. Release of calcium from internal stores mimics the effect of extracellular calcium. It is proposed that calcium stores modulate excitability of central neurons.

scholarly journals Relocalization of STIM1 in mouse oocytes at fertilization: early involvement of store-operated calcium entry

Reproduction ◽  
2009 ◽  
Vol 138 (2) ◽  
pp. 211-221 ◽  
Author(s):  
Carolina Gómez-Fernández ◽  
Eulalia Pozo-Guisado ◽  
Miguel Gañán-Parra ◽  
Mario J Perianes ◽  
Ignacio S Álvarez ◽  
...  
Keyword(s):  
Intracellular Signaling ◽  
Calcium Entry ◽  
Calcium Stores ◽  
Calcium Waves ◽  
Resting Cells ◽  
Metaphase Arrest ◽  
Mouse Oocytes ◽  
Store Depletion ◽  
Store Operated Calcium Entry ◽  
Mature Mouse

Calcium waves represent one of the most important intracellular signaling events in oocytes at fertilization required for the exit from metaphase arrest and the resumption of the cell cycle. The molecular mechanism ruling this signaling has been described in terms of the contribution of intracellular calcium stores to calcium spikes. In this work, we considered the possible contribution of store-operated calcium entry (SOCE) to this signaling, by studying the localization of the protein STIM1 in oocytes. STIM1 has been suggested to play a key role in the recruitment and activation of plasma membrane calcium channels, and we show here that mature mouse oocytes express this protein distributed in discrete clusters throughout their periphery in resting cells, colocalizing with the endoplasmic reticulum marker calreticulin. However, immunolocalization of the endogenous STIM1 showed considerable redistribution over larger areas or patches covering the entire periphery of the oocyte during Ca2+ store depletion induced with thapsigargin or ionomycin. Furthermore, pharmacological activation of endogenous phospholipase C induced a similar pattern of redistribution of STIM1 in the oocyte. Finally, fertilization of mouse oocytes revealed a significant and rapid relocalization of STIM1, similar to that found after pharmacological Ca2+ store depletion. This particular relocalization supports a role for STIM1 and SOCE in the calcium signaling during early stages of fertilization.

scholarly journals Store-operated calcium entry in physiology and pathology of mammalian cells.

2005 ◽  
Vol 52 (2) ◽  
pp. 397-409 ◽  
Author(s):  
Berenika Targos ◽  
Jolanta Barańska ◽  
Paweł Pomorski
Keyword(s):  
Cell Cycle ◽  
Calcium Level ◽  
Mammalian Cells ◽  
Long Term Potentiation ◽  
Calcium Entry ◽  
Neuroendocrine Cells ◽  
Calcium Stores ◽  
Excitable Cells ◽  
Store Operated Calcium Entry ◽  
Er Calcium

One of the numerous calcium-involving processes in mammalian cells is store-operated calcium entry (SOCE) -- the process in which depletion of calcium stores in the endoplasmic reticulum (ER) induces calcium influx from the extracellular space. Previously supposed to function only in non-excitable cells, SOCE is now known to play a role also in such excitable cells as neurons, muscles and neuroendocrine cells and is found in many different cell types. SOCE participates not only in processes dependent on ER calcium level but also specifically regulates some important processes such as cAMP production, T lymphocyte activation or induction of long-term potentiation. Impairment of SOCE can be an element of numerous disorders such as acute pancreatitis, primary immunodeficiency and, since it can take part in apoptosis or cell cycle regulation, SOCE may also be partially responsible for such serious disorders as Alzheimer disease and many types of cancer. Even disturbances in the 'servant' role of maintaining ER calcium level may cause serious effects because they can lead to ER homeostasis disturbance, influencing gene expression, protein synthesis and processing, and the cell cycle.

scholarly journals Nanoscale organization and calcium influx in dendritic spines guarantee ER store refilling without depletion

2021 ◽  
Author(s):  
Kanishka Basnayake ◽  
David Mazaud ◽  
Lilia Kushnireva ◽  
Alexis Bemelmans ◽  
nathalie Rouach ◽  
...  
Keyword(s):  
Dendritic Spines ◽  
Plasma Membranes ◽  
Calcium Release ◽  
Calcium Influx ◽  
Smooth Endoplasmic Reticulum ◽  
Super Resolution ◽  
Calcium Stores ◽  
Calcium Dynamics ◽  
Store Operated Calcium Entry ◽  
Critical Components

Dendritic spines are critical components of the neuronal synapse as they receive and transform the synaptic input into a succession of biochemical events regulated by calcium signaling. The spine apparatus (SA), an extension of smooth endoplasmic reticulum (ER), regulates slow and fast calcium dynamics in spines. Calcium release events from SA result in a rapid depletion of calcium ion reservoir, yet the next cycle of signaling requires replenishment of SA calcium stores. How dendritic spines achieve this without triggering calcium release remains unclear. Using computational modeling, calcium and STED super-resolution imaging, we showed that the refilling of calcium-deprived SA involves store-operated calcium entry during spontaneous calcium transients in spine heads. We identified two main conditions that guarantee SA replenishment without depletion: (1) a small amplitude and slow timescale for calcium influx, and (2) a close proximity between SA and plasma membranes. Thereby, molecular nano-organization creates the conditions for a clear separation between SA replenishment and depletion. We further conclude that the nanoscale organization of SA receptors underlies the specificity of calcium dynamics patterns during the induction of long-term synaptic changes.

Impairment of Store-operated Calcium Entry: Implications in Alzheimer’s Neurodegeneration

2021 ◽  
Vol 17 (12) ◽  
pp. 1088-1094
Author(s):  
Jing Zhou ◽  
Shengzhou Wu
Keyword(s):  
Endoplasmic Reticulum ◽  
Neurodegenerative Disorder ◽  
Therapeutic Potential ◽  
Alternative Hypothesis ◽  
Cholinergic Neurons ◽  
Proteasome Inhibition ◽  
Calcium Entry ◽  
Calcium Sensors ◽  
Store Operated Calcium Entry ◽  
Er Calcium

Alzheimer's disease (AD) is an insidious and progressive neurodegenerative disorder. Dysfunction of central cholinergic neurons, amyloid aggregation and deposition,oxidative stress,and biometal dyshomeostasis has been regarded as the major pathogenic mediators in this devastating disease. However, strategies derived from these hypotheses fail to slow down or stop the progression of AD, warranting a combination of therapies to target multiple etiological factors or examining alternative hypothesis. Store-operated calcium entry (SOCE) is the process by which depletion of calcium in the endoplasmic reticulum (ER) lumen causes an influx of calcium across plasmalemma. Accumulating evidence indicates that neuronal SOCE (nSOCE) is inhibited in family AD (FAD) and the inhibition of which causes instability of dendritic spines and enhances amyloidogenesis. Mutant Presenilin fails to function as an ER calcium leak channel and promotes degradation of stromal interaction molecules (STIM), ER calcium sensors; these effects may account for the repression of nSOCE in FAD. We have demonstrated that activation of autophagy degrades STIM proteins, resulting in a trimming effect on a dendritic arbor, under proteasome inhibition and endoplasmic reticulum stress, which are intimately connected with AD. Thus, we hypothesize that autophagy represses SOCE by degrading STIM proteins, leading to synapse loss in AD. This review article will highlight the roles of SOCE in AD neurodegeneration, the degradative mechanisms of STIM protein, and the therapeutic potential and associated challenge.

Store-operated calcium entry and increased endothelial cell permeability

2000 ◽  
Vol 279 (5) ◽  
pp. L815-L824 ◽  
Author(s):  
Natalie Norwood ◽  
Timothy M. Moore ◽  
David A. Dean ◽  
Rakesh Bhattacharjee ◽  
Ming Li ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Calcium Current ◽  
Calcium Release ◽  
Calcium Entry ◽  
Extracellular Calcium ◽  
Cell Permeability ◽  
Calcium Stores ◽  
Store Depletion ◽  
Endothelial Cell Permeability ◽  
Store Operated Calcium Entry

We hypothesized that myosin light chain kinase (MLCK) links calcium release to activation of store-operated calcium entry, which is important for control of the endothelial cell barrier. Acute inhibition of MLCK caused calcium release from inositol trisphosphate-sensitive calcium stores and prevented subsequent activation of store-operated calcium entry by thapsigargin, suggesting that MLCK serves as an important mechanism linking store depletion to activation of membrane calcium channels. Moreover, in voltage-clamped single rat pulmonary artery endothelial cells, thapsigargin activated an inward calcium current that was abolished by MLCK inhibition. F-actin disruption activated a calcium current, and F-actin stabilization eliminated the thapsigargin-induced current. Thapsigargin increased endothelial cell permeability in the presence, but not in the absence, of extracellular calcium, indicating the importance of calcium entry in decreasing barrier function. Although MLCK inhibition prevented thapsigargin from stimulating calcium entry, it did not prevent thapsigargin from increasing permeability. Rather, inhibition of MLCK activity increased permeability that was especially prominent in low extracellular calcium. In conclusion, MLCK links store depletion to activation of a store-operated calcium entry channel. However, inhibition of calcium entry by MLCK is not sufficient to prevent thapsigargin from increasing endothelial cell permeability.

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