scholarly journals Effect of caffeine and coffee diets on calcium signalling in rat hippocampal neurons

2021 ◽  
Vol 67 (4) ◽  
pp. 37-43
Author(s):  
V.M. Shkryl ◽  
◽  
T.G. Turytska ◽  
V.A. Yavorsky ◽  
V.P. Lyashenko ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Calcium Level ◽  
Hippocampal Neurons ◽  
Ryanodine Receptors ◽  
Calcium Signalling ◽  
Membrane Depolarization ◽  
Calcium Mobilization ◽  
High Concentration ◽  
Excitability Of Neurons

The effects of long-lasting high concentration coffee and caffeine diets on calcium mobilization in rat hippocampal neurons were studied. Changes in the basal calcium level in the hippocampal neurons of control and experimental rats kept on a coffee or caffeine diet were measured. We also recorded the changes in the Ca2+ transients’ amplitude evoked by membrane depolarization or emptying the Ca2+ depot of the endoplasmic reticulum (ER) induced by caffeine activator of the ryanodine receptors. In rats on a coffee or caffeine diet, the basal Ca2+ level was increased by 7.4% and 11%, respectively, compared to control animals. In these groups, the amplitude of Ca2+ transients increased by 70% and 90%, respectively, of the basal level in response to the membrane depolarization. In the same groups, the amount of Ca2+ released from the ER was increased by two and three times, respectively, compared to the control after activation of ryanodine receptors. We concluded that long-term coffee and caffeine diets in rats cause a significant disruption of the hippocampal neurons’ endoplasmic reticulum function. The diets evoke an increase in Ca2+ concentration in the neurons and an excessive release of Ca2+ in response to excitation. The latter can lead to increased excitability of neurons and their further death from excessive Ca2+ levels.

scholarly journals Increased excitability in hippocampal neurons of synaptopodin-knockout mouse

2021 ◽  
Author(s):  
Etay Aloni ◽  
Serphima Verbitzky ◽  
Lilia kushnireva ◽  
Eduard Korkotian ◽  
Menahem Segal
Keyword(s):  
Endoplasmic Reticulum ◽  
Hippocampal Neurons ◽  
Dorsal Hippocampus ◽  
Long Term Potentiation ◽  
Ca1 Neurons ◽  
Ca1 Region ◽  
Term Potentiation ◽  
Hippocampus Slice ◽  
Recorded Activity

Abstract Synaptopodin (SP) is localized within the spine apparatus, an enigmatic structure located in the neck of spines of central excitatory neurons. It serves as a link between the spine head, where the synapse is located, and the endoplasmic reticulum (ER) in the parent dendrite (Vlachos et al. 2009, Korkotian and Segal, 2011, Zhang et al. 2013). SP is also located in the axon initial segment, in association with the cisternal organelle, another structure related to endoplasmic reticulum. Extensive research using SP knockout (SPKO) mice suggests that SP has a pivotal role in structural and functional plasticity (Deller et al. 2003, Deller et al. 2007). Consequently, SPKO mice were shown to be deficient in cognitive functions, and in ability to undergo long term potentiation of reactivity to afferent stimulation (Deller et al. 2003). In contrast, neurons of SPKO mice appear to be more excitable than their wild type (wt) counterparts(Bas Orth et al, 2007). To address this discrepancy, we have now recorded activity of CA1 neurons in the mouse hippocampus slice, with both extracellular and patch recording methods. Electrophysiologically, SPKO cells in CA1 region of the dorsal hippocampus were more excitable than wt ones. In addition, exposure of mice to a complex environment caused a higher proportion of arc-expressing cells in SPKO than in wt mice hippocampus. These experiments indicate that higher excitability and higher expression of arc staining may reflect SP deficiency in the hippocampus of adult SPKO mice.

scholarly journals Intracellular Ca2+ stores can account for the time course of LTP induction: a model of Ca2+ dynamics in dendritic spines

1995 ◽  
Vol 74 (3) ◽  
pp. 1046-1055 ◽  
Author(s):  
A. Schiegg ◽  
W. Gerstner ◽  
R. Ritz ◽  
J. L. van Hemmen
Keyword(s):  
Hippocampal Neurons ◽  
Time Course ◽  
Calcium Release ◽  
Model Simulation ◽  
Ryanodine Receptors ◽  
Long Term Potentiation ◽  
Calcium Stores ◽  
Calcium Source ◽  
The One

1. A model of Ca2+ dynamics in spines of CA1 hippocampal neurons is presented. In contrast to traditional models, which concentrate on the effects of Ca2+ influx, diffusion, buffering, and extrusion, we also consider the additional effect of intracellular Ca2+ stores. 2. It is shown that traditional models without Ca2+ stores cannot account for the time course of long-term potentiation (LTP) induction as found in recent experiments. Experimental data suggest that the intracellular Ca2+ concentration should be elevated for up to 2 s, whereas the Ca2+ concentration in standard models of Ca2+ dynamics decays much faster. 3. When intracellular Ca2+ stores are taken into account, a much slower decay is found. In particular, a model simulation with a stimulation paradigm consisting of two bursts of four impulses at 100 Hz each and variable interburst intervals can reproduce experimental results found for primed or theta-burst stimulation. 4. In our model, Ca2+ release from the store has a nonlinear, bell-shaped dependence on the intracellular Ca2+ concentration, similar to the one found for inositoltrisphosphate and ryanodine receptors. These receptors are known to control calcium release from intracellular stores. 5. Our model suggests an important role of intracellular calcium stores in the induction of LTP. The stores serve as a long-term calcium source that can sustain an intracellular Ca2+ concentration above the resting level for 1-2 s.

Calcium signalling in early divergence of Metazoa: mechanisms involved in the control of muscle-like cell contraction in Hydra plagiodesmica

2019 ◽  
Vol 97 (9) ◽  
pp. 812-824 ◽  
Author(s):  
María Eugenia Alzugaray ◽  
María Victoria Gavazzi ◽  
Jorge Rafael Ronderos
Keyword(s):  
Endoplasmic Reticulum ◽  
Homo Sapiens ◽  
Ryanodine Receptors ◽  
Calcium Signalling ◽  
Cell Contraction ◽  
Inositol 1,4,5 Trisphosphate ◽  
Trisphosphate Receptor

Our laboratory has previously examined the effect of neuropeptides on the activity of the hypostome of the hydra Hydra plagiodesmica Dioni, 1968 (Cnidaria: Hydrozoa). These results showed that the hypostome, a structure extruded during feeding, responds to myoregulatory peptides and that this mechanism might be regulated by changes in the cytosolic levels of calcium (Ca2+). We analyse now the ways in which Ca2+ modulates hypostome activity during feeding. The use of calcium chelators confirms that Ca2+ is relevant in inducing hypostome extrusion. The assay of compounds that modulate the activity of Ca2+ channels in the endoplasmic reticulum suggests that, beyond the extracellular influx of calcium, intracellular sources of the ion are involved and might include both ryanodine receptors (RyR) and the inositol 1,4,5-trisphosphate receptor (IP3R). Bioinformatic searches based on sequences of RyR and IP3R of humans (Homo sapiens Linnaeus, 1758) show that IP3Rs are present in all groups analysed, including Fungi and Choanoflagellata. Although H. plagiodesmica responds to caffeine and ryanodine, which are known to modulate RyRs, this family of receptors seems not to be predicted in Cnidaria, suggesting that this phylum either lacks these kinds of channels or that they possess a different structure compared with those possessed by other Metazoa.

scholarly journals Single-cell temperature mapping with fluorescent thermometer nanosheets

2020 ◽  
Vol 152 (8) ◽  
Author(s):  
Kotaro Oyama ◽  
Mizuho Gotoh ◽  
Yuji Hosaka ◽  
Tomoko G. Oyama ◽  
Aya Kubonoya ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Hippocampal Neurons ◽  
Single Cells ◽  
Ryanodine Receptors ◽  
Hek293 Cells ◽  
Temperature Sensitive ◽  
Mitochondrial Uncoupling ◽  
Brown Adipocytes ◽  
Temperature Mapping ◽  
Neonatal Cardiomyocytes

Recent studies using intracellular thermometers have shown that the temperature inside cultured single cells varies heterogeneously on the order of 1°C. However, the reliability of intracellular thermometry has been challenged both experimentally and theoretically because it is, in principle, exceedingly difficult to exclude the effects of nonthermal factors on the thermometers. To accurately measure cellular temperatures from outside of cells, we developed novel thermometry with fluorescent thermometer nanosheets, allowing for noninvasive global temperature mapping of cultured single cells. Various types of cells, i.e., HeLa/HEK293 cells, brown adipocytes, cardiomyocytes, and neurons, were cultured on nanosheets containing the temperature-sensitive fluorescent dye europium (III) thenoyltrifluoroacetonate trihydrate. First, we found that the difference in temperature on the nanosheet between nonexcitable HeLa/HEK293 cells and the culture medium was less than 0.2°C. The expression of mutated type 1 ryanodine receptors (R164C or Y523S) in HEK293 cells that cause Ca2+ leak from the endoplasmic reticulum did not change the cellular temperature greater than 0.1°C. Yet intracellular thermometry detected an increase in temperature of greater than ∼2°C at the endoplasmic reticulum in HeLa cells upon ionomycin-induced intracellular Ca2+ burst; global cellular temperature remained nearly constant within ±0.2°C. When rat neonatal cardiomyocytes or brown adipocytes were stimulated by a mitochondrial uncoupling reagent, the temperature was nearly unchanged within ±0.1°C. In cardiomyocytes, the temperature was stable within ±0.01°C during contractions when electrically stimulated at 2 Hz. Similarly, when rat hippocampal neurons were electrically stimulated at 0.25 Hz, the temperature was stable within ±0.03°C. The present findings with nonexcitable and excitable cells demonstrate that heat produced upon activation in single cells does not uniformly increase cellular temperature on a global basis, but merely forms a local temperature gradient on the order of ∼1°C just proximal to a heat source, such as the endoplasmic/sarcoplasmic reticulum ATPase.

Neuregulin β1 enhances peak glutamate-induced intracellular calcium levels through endoplasmic reticulum calcium release in cultured hippocampal neuronsThis article is one of a selection of papers published in a special issue celebrating the 125th anniversary of the Faculty of Medicine at the University of Manitoba.

2009 ◽  
Vol 87 (10) ◽  
pp. 883-891 ◽  
Author(s):  
Jason Schapansky ◽  
Marc Morissette ◽  
Gary Odero ◽  
Benedict Albensi ◽  
Gordon Glazner
Keyword(s):  
Endoplasmic Reticulum ◽  
Intracellular Calcium ◽  
Glutamate Receptors ◽  
Metabotropic Glutamate Receptors ◽  
Calcium Release ◽  
Ryanodine Receptors ◽  
Intracellular Free Calcium ◽  
Free Calcium ◽  
Metabotropic Glutamate

Modulation of intracellular free calcium levels is the primary second messenger system of the neuronal glutamatergic system, playing a role in regulation of all major cellular processes. The protein neuregulin (NRG) β1 acts as an extracellular signaling ligand in neurons, rapidly regulating currents through ionotropic glutamate receptors. The effect NRG may have on glutamate-induced changes in intracellular free calcium concentrations has not been examined, however. In this study, cultured embryonic rat hippocampal neurons were treated with NRGβ1 to determine a possible effect on glutamate-induced intracellular calcium levels. Long-term (24 h), but not short-term (1 h), incubation with NRGβ1 resulted in a significantly greater glutamate-mediated acute peak elevation of intracellular calcium levels than occurred in vehicle-treated neurons. Long-term NRGβ1 incubation significantly enhanced calcium increase induced by specific stimulation of metabotropic glutamate receptors, but did not significantly alter the N-methyl d-aspartate (NMDA)- or KCl-induced calcium increase and paradoxically decreased the effect of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) treatment on intracellular calcium. Metabotropic glutamate receptors cause increased intracellular free calcium via release of calcium from intracellular stores; thus this system was examined in more detail. NRGβ1 treatment significantly (greater than 2-fold) enhanced calcium release from endoplasmic reticulum stores after stimulation of ryanodine receptors with caffeine, but did not significantly increase calcium release from endoplasmic reticulum mediated by inositol trisphosphate (IP3) receptors. In addition, ryanodine receptor inhibition with ruthenium red prevented the glutamate-induced increase in intracellular calcium levels in NRGβ1-treated neurons. These data show that long-term NRGβ1 treatment can enhance glutamate-induced peak intracellular calcium levels through metabotropic glutamate receptor activation by increasing endoplasmic reticulum calcium release through ryanodine receptors.

scholarly journals Thiol oxidation by 2,2′-dithiodipyridine causes a reversible increase in cytoplasmic free Ca2+ concentration in pancreatic β-cells. Role for inositol 1,4,5-trisphosphate-sensitive Ca2+ stores

1997 ◽  
Vol 321 (2) ◽  
pp. 347-354 ◽  
Author(s):  
Md. Shahidul ISLAM ◽  
Henrik KINDMARK ◽  
Olof LARSSON ◽  
Per-Olof BERGGREN
Keyword(s):  
Ryanodine Receptors ◽  
Membrane Depolarization ◽  
Thiol Oxidation ◽  
High Concentration ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Patch Clamp Technique ◽  
Mitochondrial Inner Membrane ◽  
Patch Configuration ◽  
Ca2 Channels

2,2ƀ-Dithiodipyridine (2,2ƀ-DTDP), a reactive disulphide that mobilizes Ca2+ from ryanodine-sensitive Ca2+ stores in muscle, induced a biphasic increase in cytoplasmic free Ca2+ concentration ([Ca2+]i) in pancreatic α-cells loaded with fura 2. This increase consisted of an early transient followed by a second, slower, rise. The [Ca2+]i transient was dependent on extracellular Ca2+ and disappeared on treatment with nimodipine. The reactive disulphide caused plasma membrane depolarization, as studied by the perforated-patch configuration of the patch-clamp technique. Hence membrane depolarization and opening of the L-type voltage-gated Ca2+ channels were responsible for the first transient in [Ca2+]i. The second slower increase in [Ca2+]i was prolonged but readily reversed by the disulphide-reducing agent 1,4-dithiothreitol. This increase in [Ca2+]i was not decreased by nimodipine or by omission of extracellular Ca2+, but was eliminated when the Ins(1,4,5)P3-sensitive Ca2+ pool was first depleted by carbachol. Ryanodine or its α-alanyl analogue did not release Ca2+ from intracellular stores, and a high concentration of ryanodine did not inhibit Ca2+ release by 2,2ƀ-DTDP. The disulphide compound suppressed glucose metabolism and decreased the mitochondrial inner-membrane potential. We conclude that thiol oxidation by 2,2ƀ-DTDP affects Ca2+ homeostasis in α-cells by multiple mechanisms. However, unlike the situation in muscle, in α-cells 2,2ƀ-DTDP releases Ca2+ from intracellular pools by mechanisms that do not involve activation of ryanodine receptors. Instead, in these cells the Ins(1,4,5)P3-sensitive intracellular Ca2+ store comprises an alternative target for the Ca2+-mobilizing action of the reactive disulphide compound.

Induction of LTD in the Dentate Gyrus In Vitro Is NMDA Receptor Independent, but Dependent on Ca2+ Influx via Low-Voltage–Activated Ca2+ Channels and Release of Ca2+ From Intracellular Stores

1997 ◽  
Vol 77 (2) ◽  
pp. 812-825 ◽  
Author(s):  
Yue Wang ◽  
Michael J. Rowan ◽  
Roger Anwyl
Keyword(s):  
Nmda Receptor ◽  
Dentate Gyrus ◽  
Low Voltage ◽  
Ryanodine Receptors ◽  
Long Term Potentiation ◽  
Ruthenium Red ◽  
High Concentration ◽  
Intracellular Ca

Wang, Yue, Michael J. Rowan, and Roger Anwyl. Induction of LTD in the dentate gyrus in vitro is NMDA receptor independent, but dependent on Ca2+ influx via low-voltage-activated Ca2+ channels and release of Ca2+ from intracellular stores. J. Neurophysiol. 77: 812–825, 1997. The mechanisms of the induction of long-term depression (LTD) of field excitatory postsynaptic potentials (EPSPs) and whole cell patch-clamped excitatory postsynaptic currents (EPSCs) were studied in the dentate gyrus of the rat hippocampus. LTD of field EPSPs measuring 40% of control at 30 min poststimulation was induced by low-frequency stimulation consisting of 900 pulses at 1 Hz. LTD of EPSCs measuring 37% of control was induced by a pairing procedure consisting of 60 pulses at 1 Hz applied under voltage clamp at a holding potential of −40 mV. The induction of LTD of field EPSPs was dependent on an influx of extracellular calcium, being reduced in a low-Ca2+ (0.8 mM) medium. However, substantial LTD (26%) was still induced in such a medium, demonstrating the relatively low sensitivity of LTD induction to the level of extracellular Ca2+. A high concentration of the N-methyl-d-aspartate receptor antagonist d(−)-2-amino-5-phosphonopentanoic acid (d-AP5) (100 μM) did not significantly inhibit the induction of LTD of EPSCs evoked by the intracellular pairing procedure. d-AP5 partially reduced the magnitude of LTD of field EPSPs, but substantial LTD was still induced in the presence of AP5. The induction of LTD was strongly inhibited by Ni2+ (50 μM) but not by nifedipine (10 μM), indicating that Ca2+ influx via T-type, but not L-type, Ca2+ channels is required for the induction of LTD. The induction of LTD was strongly inhibited by thapsigargin, an agent known to deplete intracellular Ca2+ stores. The induction of LTD, but not long-term potentiation (LTP), was also strongly inhibited by ruthenium red, an agent known to block the ryanodine receptors located on intracellular Ca2+ stores. These results demonstrate that Ca2+ release from intracellular Ca2+ stores is required for the induction of LTD, but not LTP. The results of the present experiments suggest that the induction of LTD involves the entry of Ca2+ via low-voltage–activated voltage-gated Ca2+ channels followed by release of Ca2+ from intracellular ryanodine-receptor-sensitive Ca2+ stores.

Increase associated risk of gynaecological cancer due to long-term exposure to high concentration of atmospheric SO2 industrial pollutant

2021 ◽  
pp. 1420326X2110036
Author(s):  
Qian Xu ◽  
Chan Lu ◽  
Rachael Gakii Murithi ◽  
Lanqin Cao
Keyword(s):  
Time Windows ◽  
Air Pollutant ◽  
Gynaecological Cancer ◽  
High Concentration ◽  
The Past ◽  
Short And Long Term ◽  
Using Data ◽  
Air Quality Monitoring Stations ◽  
Control Study

A cohort case–control study was conducted in XiangYa Hospital, Changsha, China, which involved 305 patients and 399 healthy women, from June 2010 to December 2018, to evaluate the association between Chinese women’s short- and long-term exposure to industrial air pollutant, SO2 and gynaecological cancer (GC). We obtained personal and family information from the XiangYa Hospital electronic computer medical records. Using data obtained from the air quality monitoring stations in Changsha, we estimated each woman’s exposure to the industrial air pollutant, sulphur dioxide (SO2), for different time windows, including the past 1, 5, 10 and 15 years before diagnosis of the disease. A multiple logistic regression model was used to assess the association between GC and SO2 exposure. GC was significantly associated with long-term SO2 exposure, with adjusted odds ratio (95% confidence interval) = 1.56 (1.10–2.21) and 1.81 (1.07–3.06) for a per interquartile range increase in the past 10 and 15 years, respectively. Sensitivity analysis showed that different groups reacted in different ways to long-term SO2 exposure. We concluded that long-term exposure to high concentration of industrial pollutant, SO2 is associated with the development of GC. This finding has implications for the prevention and reduction of GC.

scholarly journals Self-buffering capacity of a human sulfatase for central nervous system delivery

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yi Wen ◽  
Nazila Salamat-Miller ◽  
Keethkumar Jain ◽  
Katherine Taylor
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Buffering Capacity ◽  
The Self ◽  
High Concentration ◽  
Formulation Design ◽  
The Central Nervous System ◽  
Therapeutic Enzymes ◽  
Intrathecal Space

AbstractDirect delivery of therapeutic enzymes to the Central Nervous System requires stringent formulation design. Not only should the formulation design consider the delicate balance of existing ions, proteins, and osmolality in the cerebrospinal fluid, it must also provide long term efficacy and stability for the enzyme. One fundamental approach to this predicament is designing formulations with no buffering species. In this study, we report a high concentration, saline-based formulation for a human sulfatase for its delivery into the intrathecal space. A high concentration formulation (≤ 40 mg/mL) was developed through a series of systematic studies that demonstrated the feasibility of a self-buffered formulation for this molecule. The self-buffering capacity phenomenon was found to be a product of both the protein itself and potentially the residual phosphates associated with the protein. To date, the self-buffered formulation for this molecule has been stable for up to 4 years when stored at 5 ± 3 °C, with no changes either in the pH values or other quality attributes of the molecule. The high concentration self-buffered protein formulation was also observed to be stable when exposed to multiple freeze–thaw cycles and was robust during in-use and agitation studies.

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