Different Types Of Ca2 Research Articles

Between bodily action and conventionalized structure: The neural mechanisms of constructed action in sign language comprehension

Sign languages (SLs) are expressed through different bodily actions, ranging from re-enactment of physical events (constructed action, CA) to sequences of lexical signs with internal structure (plain telling, PT). Despite the prevalence of CA in signed interactions and its significance for SL comprehension, its neural dynamics remain unexplored. We examined the processing of different types of CA (subtle, reduced, and overt) and PT in 35 adult deaf or hearing native signers. The electroencephalographic-based processing of signed sentences with incongruent targets was recorded. Attenuated N300 and early N400 were observed for CA in deaf but not in hearing signers. No differences were found between sentences with CA types in all signers, suggesting a continuum from PT to overt CA. Deaf signers focused more on body movements; hearing signers on faces. We conclude that CA is processed less effortlessly than PT, arguably because of its strong focus on bodily actions.

Relationship between chorioamnionitis or funisitis and lung injury among preterm infants: meta-analysis involved 16 observational studies with 68,397 participants

BackgroundChorioamnionitis (CA) can cause multiple organ injuries in premature neonates, particularly to the lungs. Different opinions exist regarding the impact of intrauterine inflammation on neonatal respiratory distress syndrome (NRDS) and bronchopulmonary dysplasia (BPD). We aim to systematically review the relationship between CA or Funisitis (FV) and lung injury among preterm infants.MethodsWe electronically searched PubMed, EMbase, the Cochrane library, CNKI, and CMB for cohort studies from their inception to March 15, 2023. Two reviewers independently screened literature, gathered data, and did NOS scale of included studies. The meta-analysis was performed using RevMan 5.3.ResultsSixteen observational studies including 68,397 patients were collected. Meta-analysis showed CA or FV increased the lung injury risk (OR = 1.43, 95%CI: 1.06–1.92). Except for histological chorioamnionitis (HCA) (OR = 0.72, 95%CI: 0.57–0.90), neither clinical chorioamnionitis (CCA) (OR = 1.86, 95%CI: 0.93–3.72) nor FV (OR = 1.23, 95%CI: 0.48–3.15) nor HCA with FV (OR = 1.85, 95%CI: 0.15–22.63) had statistical significance in NRDS incidence. As a result of stratification by grade of HCA, HCA (II) has a significant association with decreased incidence of NRDS (OR = 0.48, 95%CI: 0.35–0.65). In terms of BPD, there is a positive correlation between BPD and CA/FV (CA: OR = 3.18, 95%CI: 1.68–6.03; FV: OR = 6.36, 95%CI: 2.45–16.52). Among CA, HCA was positively associated with BPD (OR = 2.70, 95%CI: 2.38–3.07), whereas CCA was not associated with BPD (OR = 2.77, 95%CI: 0.68–11.21). HCA and moderate to severe BPD (OR = 25.38, 95%CI: 7.13–90.32) showed a positive correlation, while mild BPD (OR = 2.29, 95%CI: 0.99–5.31) did not.ConclusionCurrently, evidence suggests that CA or FV increases the lung injury incidence in premature infants. For different types of CA and FV, HCA can increase the incidence of BPD while decreasing the incidence of NRDS. And this “protective effect” only applies to infants under 32 weeks of age. Regarding lung injury severity, only moderate to severe cases of BPD were positively correlated with CA.

Size-Dependent Cytoprotective Effects of Selenium Nanoparticles during Oxygen-Glucose Deprivation in Brain Cortical Cells.

It is known that selenium nanoparticles (SeNPs) obtained on their basis have a pleiotropic effect, inducing the process of apoptosis in tumor cells, on the one hand, and protecting healthy tissue cells from death under stress, on the other hand. It has been established that SeNPs protect brain cells from ischemia/reoxygenation through activation of the Ca2+ signaling system of astrocytes and reactive astrogliosis. At the same time, for a number of particles, the limitations of their use, associated with their size, are shown. The use of nanoparticles with a diameter of less than 10 nm leads to their short life-time in the bloodstream and rapid removal by the liver. Nanoparticles larger than 200 nm activate the complement system and are also quickly removed from the blood. The effects of different-sized SeNPs on brain cells have hardly been studied. Using the laser ablation method, we obtained SeNPs of various diameters: 50 nm, 100 nm, and 400 nm. Using fluorescence microscopy, vitality tests, PCR analysis, and immunocytochemistry, it was shown that all three types of the different-sized SeNPs have a cytoprotective effect on brain cortex cells under conditions of oxygen-glucose deprivation (OGD) and reoxygenation (R), suppressing the processes of necrotic death and inhibiting different efficiency processes of apoptosis. All of the studied SeNPs activate the Ca2+ signaling system of astrocytes, while simultaneously inducing different types of Ca2+ signals. SeNPs sized at 50 nm- induce Ca2+ responses of astrocytes in the form of a gradual irreversible increase in the concentration of cytosolic Ca2+ ([Ca2+]i), 100 nm-sized SeNPs induce stable Ca2+ oscillations without increasing the base level of [Ca2+]i, and 400 nm-sized SeNPs cause mixed patterns of Ca2+ signals. Such differences in the level of astrocyte Ca2+ signaling can explain the different cytoprotective efficacy of SeNPs, which is expressed in the expression of protective proteins and the activation of reactive astrogliosis. In terms of the cytoprotective efficiency under OGD/R conditions, different-sized SeNPs can be arranged in descending order: 100 nm-sized > 400 nm-sized > 50 nm-sized.

A Discriptive Study on the Efficacy of Doxycycline for Pleurodesis in Malignant Pleural Effusions

Objective: The purpose of this study was to determine the efficacy of Doxycycline for pleurodesis in cases of malignant pleural effusions. Subject and Methods; This was a descriptive case study conducted at Sheikh Zayed Hospital Rahim Yar Khan during the period of May 2021 to November 2021. In this study the diagnosed cases of malignant pleural effusion, irrespective of its type and metastasis in adult age range were included of both genders. The pleural effusion was effectively drained with appropriate chest drain. After complete drainage assessed by X ray chest PA view, 10 capsules of Doxycycline (100 mg) were diluted in 50 ml normal saline and were injected through chest drain and clamped for 24 hours. Paracetamol was given as analgesia. The drain was re opened after 24 hours and were followed by X ray chest to label for any fluid presence. Efficacy was lapelled as yes where there was no fluid on x ray and drain output was less than 50 ml. Results: In this study, there were total 40 cases of malignant pleural effusion of any type. Out of these 22 (62%) were females and 18 (34%) males. The mean age was 52.39±9.13 years. Regarding different types of CA, the most common was CA breast comprising 30 (60%) of the cases followed by lung cancer seen in 15 (30%) of cases. The efficacy of Doxycycline for pleurodesis was observed in 22 (56%) of cases. The efficacy was observed in 12 (72.73%) cases with effusion less than 1 liter with p= 0.01. There was no significant difference in terms of duration of pleural effusion where it was seen in 55% of cases with effusion more than 1 month and 60% of cases with duration less than this with p= 0.83. Conclusion: Doxycycline has shown its efficacy for pleurodesis in almost half of the cases. Keywords: Doxycycline, Pleurodesis, Fever, Pulmonology, Epidemiological

Systematic Review of Calcium Channels and Intracellular Calcium Signaling: Relevance to Pesticide Neurotoxicity.

Pesticides of different chemical classes exert their toxic effects on the nervous system by acting on the different regulatory mechanisms of calcium (Ca2+) homeostasis. Pesticides have been shown to alter Ca2+ homeostasis, mainly by increasing its intracellular concentration above physiological levels. The pesticide-induced Ca2+ overload occurs through two main mechanisms: the entry of Ca2+ from the extracellular medium through the different types of Ca2+ channels present in the plasma membrane or its release into the cytoplasm from intracellular stocks, mainly from the endoplasmic reticulum. It has also been observed that intracellular increases in the Ca2+ concentrations are maintained over time, because pesticides inhibit the enzymes involved in reducing its levels. Thus, the alteration of Ca2+ levels can lead to the activation of various signaling pathways that generate oxidative stress, neuroinflammation and, finally, neuronal death. In this review, we also discuss some proposed strategies to counteract the detrimental effects of pesticides on Ca2+ homeostasis.

Structural analysis of regulatory stress elements in OsCIPK14 the rice homologue and functional validation in wheat

A major mechanism of stress tolerance in plants is to increase the cytosolic concentration of Ca2+ ion, a secondary messenger that mediates cellular responsiveness to the extracellular environment. The involvement of different types of Ca2+-sensing protein kinases such as CIPK in stress responses has been elucidated in different plant models. In this study, the upstream regulatory sequence of a CIPK homologue from an Egyptian rice cultivar (Oryza sativa cv Giza182) was structurally and functionally characterized and tested for its ability to drive the expression of β- glucuronidase reporter gene (uidA) in wheat. To that end, a 1275-bp DNA fragment, 49 nucleotides upstream of the putative transcription start site (TSS) of the OsCIPK14 coding sequence, referred in this study as URS-CIPK14, was cloned, sequenced and analyzed for the presence of stress-responsiveness cis-acting elements. Subsequently, the URS-CIPK14 was fused to the uidA gene with and without the Act-1 intron, cloned in pAB6 and transformed into wheat mature embryo for transient expression. Our results showed that URS-OsCIPK14 fused with the Act-1 intron was induced by NaCl and ABA, whereas URS-OsCIPK14 drove expression of uidA constitutively in the absence of Act-1 intron. Furthermore, rice wide-genome screening using URS-CIPK14 sequence obtained in this study identified another homologue on chromosome 11. Unlike URS-CIPK14, which is associated with chromosome 12, this homologue located at about 1015 nucleotides upstream from the putative TSS of OsCIPK15 coding sequence. Interestingly, the 5’-UTS in CIPK14 is longer than CIPK15 and can code for a putative short ORF that contains two Casein kinase II phosphorylation motifs (SXXD). The significance of this ORF is not known at this time and needs to be elucidated in future studies. We conclude that data from this work suggest that URS-CIPK14 can be used as a promoter candidate for high expression level under both constitutive and inducible conditions.

Calcium-permeable cation channels are involved in uranium uptake in Arabidopsis thaliana

Uranium (U) is a non-essential and toxic element that is taken up by plants from the environment. The assimilation pathway of U is still unknown in plants. In this study, we provide several evidences that U is taken up by the roots of Arabidopsis thaliana through Ca2+-permeable cation channels. First, we showed that deprivation of Arabidopsis plants with calcium induces a 1.5-fold increase in the capacity of roots to accumulate U, suggesting that calcium deficiency promotes the radionuclide import pathway. Second, we showed that external calcium inhibits U accumulation in roots, suggesting a common route for the uptake of both cations. Third, we found that gadolinium, nifedipine and verapamil inhibit the absorption of U, suggesting that different types of Ca2+-permeable channels serve as a route for U uptake. Last, we showed that U bioaccumulation in Arabidopsis mutants deficient for the Ca2+-permeable channels MCA1 and ANN1 is decreased by 40%. This suggests that MCA1 and ANN1 contribute to the absorption of U in different zones and cell layers of the root. Together, our results describe for the first time the involvement of Ca2+-permeable cation channels in the cellular uptake of U.

Distinct calcium regulation of TRPM7 mechanosensitive channels at plasma membrane microdomains visualized by FRET-based single cell imaging

Transient receptor potential subfamily M member 7 (TRPM7), a mechanosensitive Ca2+ channel, plays a crucial role in intracellular Ca2+ homeostasis. However, it is currently unclear how cell mechanical cues control TRPM7 activity and its associated Ca2+ influx at plasma membrane microdomains. Using two different types of Ca2+ biosensors (Lyn-D3cpv and Kras-D3cpv) based on fluorescence resonance energy transfer, we investigate how Ca2+ influx generated by the TRPM7-specific agonist naltriben is mediated at the detergent-resistant membrane (DRM) and non-DRM regions. This study reveals that TRPM7-induced Ca2+ influx mainly occurs at the DRM, and chemically induced mechanical perturbations in the cell mechanosensitive apparatus substantially reduce Ca2+ influx through TRPM7, preferably located at the DRM. Such perturbations include the disintegration of lipid rafts, microtubules, or actomyosin filaments; the alteration of actomyosin contractility; and the inhibition of focal adhesion and Src kinases. These results suggest that the mechanical membrane environment contributes to the TRPM7 function and activity. Thus, this study provides a fundamental understanding of how the mechanical aspects of the cell membrane regulate the function of mechanosensitive channels.

Bi-component HlgC/HlgB and HlgA/HlgB γ-hemolysins from S. aureus: Modulation of Ca2+ channels activity through a differential mechanism

Staphylococcal bi-component leukotoxins known as *pore-forming toxins* induce upon a specific binding to membrane receptors, two independent cellular events in human neutrophils. First, they provoke the opening of pre-existing specific ionic channels including Ca2+ channels. Then, they form membrane pores specific to monovalent cations leading to immune cells death. Among these leukotoxins, HlgC/HlgB and HlgA/HlgB γ-hemolysins do act in synergy to induce the opening of different types of Ca2+ channels in the absence as in the presence of extracellular Ca2+. Here, we investigate the mechanism underlying the modulation of Ca2+-independent Ca2+ channels in response to both active leukotoxins in human neutrophils. In the absence of extracellular Ca2+, the Mn2+ has been used as a Ca2+ surrogate to determine the activity of Ca2+-independent Ca2+ channels. Our findings provide new insights about different mechanisms involved in the staphylococcal γ-hemolysins activity to regulate three different types of Ca2+-independent Ca2+ channels. We conclude that (i) HlgC/HlgB stimulates the opening of La3+-sensitive Ca2+ channels, through a cholera toxin-sensitive G protein, (ii) HlgA/HlgB stimulates the opening of Ca2+ channels not sensitive to La3+, through a G protein-independent process, and (iii) unlike HlgA/HlgB, HlgC/HlgB toxins prevent the opening of a new type of Ca2+ channels by phosphorylation/de-phosphorylation-dependent mechanisms.

Mitochondria determine the sequential propagation of the calcium macrodomains revealed by the super-resolution calcium lantern imaging.

Despite the wide application of super-resolution (SR) microscopy in biological studies of cells, the technology is rarely used to monitor functional changes in live cells. By combining fast spinning disc-confocal structured illumination microscopy (SD-SIM) with loading of cytosolic fluorescent Ca2+ indicators, we have developed an SR method for visualization of regional Ca2+ dynamics and related cellular organelle morphology and dynamics, termed SR calcium lantern imaging. In COS-7 cells stimulated with ATP, we have identified various calcium macrodomains characterized by different types of Ca2+ release from endoplasmic reticulum (ER) stores. Finally, we demonstrated various roles of mitochondria in mediating calcium signals from different sources; while mitochondria can globally potentiate the Ca2+ entry associated with store release, mitochondria also locally control Ca2+ release from the neighboring ER stores and assist in their refilling processes.

A Neuromorphic Digital Circuit for Neuronal Information Encoding Using Astrocytic Calcium Oscillations.

Neurophysiological observations are clarifying how astrocytes can actively participate in information processing and how they can encode information through frequency and amplitude modulation of intracellular Ca2+ signals. Consequently, hardware realization of astrocytes is important for developing the next generation of bio-inspired computing systems. In this paper, astrocytic calcium oscillations and neuronal firing dynamics are presented by De Pittà and IF (Integrated & Fire) models, respectively. Considering highly nonlinear equations of the astrocyte model, linear approximation and single constant multiplication (SCM) techniques are employed for efficient hardware execution while maintaining the dynamic of the original models. This low-cost hardware architecture for the astrocyte model is able to show the essential features of different types of Ca2+ modulation such as amplitude modulation (AM), frequency modulation (FM), or both modes (AFM). To show good agreement between the results of original models simulated in MATLAB and the proposed digital circuits executed on FPGA, quantitative, and qualitative analyses including phase plane are done. This new neuromorphic circuit of astrocyte is able to successfully demonstrate AM/FM/AFM calcium signaling in its real operation on FPGA and has applications in self-repairing systems. It also can be employed as a subsystem for linking biological cells to artificial neuronal networks using astrocytic calcium oscillations in future research.

Two-photon Calcium Imaging in Neuronal Dendrites in Brain Slices.

Calcium (Ca2+) imaging is a powerful tool to investigate the spatiotemporal dynamics of intracellular Ca2+ signals in neuronal dendrites. Ca2+ fluctuations can occur through a variety of membrane and intracellular mechanisms and play a crucial role in the induction of synaptic plasticity and regulation of dendritic excitability. Hence, the ability to record different types of Ca2+ signals in dendritic branches is valuable for groups studying how dendrites integrate information. The advent of two-photon microscopy has made such studies significantly easier by solving the problems inherent to imaging in live tissue, such as light scattering and photodamage. Moreover, through combination of conventional electrophysiological techniques with two-photon Ca2+ imaging, it is possible to investigate local Ca2+ fluctuations in neuronal dendrites in parallel with recordings of synaptic activity in soma. Here, we describe how to use this method to study the dynamics of local Ca2+ transients (CaTs) in dendrites of GABAergic inhibitory interneurons. The method can be also applied to studying dendritic Ca2+ signaling in different neuronal types in acute brain slices.

Developmental changes in Ca2+ channel subtypes regulating endocytosis at the calyx of Held.

At the mammalian central synapse, Ca(2+) influx through Ca(2+) channels triggers neurotransmitter release by exocytosis of synaptic vesicles, which fuse with the presynaptic membrane and are subsequently retrieved by endocytosis. At the calyx of Held terminal, P/Q-type Ca(2+) channels mainly mediate exocytosis, while N- and R-type channels have a minor role in young terminals (postnatal days8-11). The role of each Ca(2+) channel subtype in endocytosis remains to be elucidated; therefore, we examined the role of each type of Ca(2+) channel in endocytosis, by using whole-cell patch-clamp recordings in conjunction with capacitance measurement techniques. We found that at the young calyx terminal, when R-type Ca(2+) channels were blocked, the slow mode of endocytosis was further slowed, while blocking of either P/Q- or N-type Ca(2+) channels had no major effect. In more mature terminals (postnatal days14-17), the slow mode of endocytosis was mainly triggered by P/Q-type Ca(2+) channels, suggesting developmental changes in the regulation of the slow mode of endocytosis by different Ca(2+) channel subtypes. In contrast, a fast mode of endocytosis was observed after strong stimulation in young terminals that was mediated mainly by P/Q-type, but not R- or N-type Ca(2+) channels. These results suggest that different types of Ca(2+) channels regulate the two different modes of endocytosis. The results may also suggest that exo- and endocytosis are regulated independently at different sites in young animals but are more tightly coupled in older animals, allowing more efficient synaptic vesicle cycling adapted for fast signalling.

Global and regional differences in cerebral blood flow after asphyxial versus ventricular fibrillation cardiac arrest in rats using ASL-MRI

Both ventricular fibrillation cardiac arrest (VFCA) and asphyxial cardiac arrest (ACA) are frequent causes of CA. However, only isolated reports compared cerebral blood flow (CBF) reperfusion patterns after different types of CA, and even fewer reports used methods that allow serial and regional assessment of CBF. We hypothesized that the reperfusion patterns of CBF will differ between individual types of experimental CA. In a prospective block-randomized study, fentanyl-anesthetized adult rats were subjected to 8min VFCA or ACA. Rats were then resuscitated with epinephrine, bicarbonate, manual chest compressions and mechanical ventilation. After the return of spontaneous circulation, CBF was then serially assessed via arterial spin-labeling magnetic resonance imaging (ASL-MRI) in cortex, thalamus, hippocampus and amygdala/piriform complex over 1h resuscitation time (RT). Both ACA and VFCA produced significant temporal and regional differences in CBF. All regions in both models showed significant changes over time (p<0.01), with early hyperperfusion and delayed hypoperfusion. ACA resulted in early hyperperfusion in cortex and thalamus (both p<0.05 vs. amygdala/piriform complex). In contrast, VFCA induced early hyperperfusion only in cortex (p<0.05 vs. other regions). Hyperperfusion was prolonged after ACA, peaking at 7min RT (RT7; 199% vs. BL, Baseline, in cortex and 201% in thalamus, p<0.05), then returning close to BL at ∼RT15. In contrast, VFCA model induced mild hyperemia, peaking at RT7 (141% vs. BL in cortex). Both ACA and VFCA showed delayed hypoperfusion (ACA, ∼30% below BL in hippocampus and amygdala/piriform complex, p<0.05; VFCA, 34–41% below BL in hippocampus and amygdala/piriform complex, p<0.05). In conclusion, both ACA and VFCA in adult rats produced significant regional and temporal differences in CBF. In ACA, hyperperfusion was most pronounced in cortex and thalamus. In VFCA, the changes were more modest, with hyperperfusion seen only in cortex. Both insults resulted in delayed hypoperfusion in all regions. Both early hyperperfusion and delayed hypoperfusion may be important therapeutic targets.This study was approved by the University of Pittsburgh IACUC 1008816-1.

Calcium regulation by temperature-sensitive transient receptor potential channels in human uveal melanoma cells

Uveal melanoma (UM) is both the most common and fatal intraocular cancer among adults worldwide. As with all types of neoplasia, changes in Ca2+ channel regulation can contribute to the onset and progression of this pathological condition. Transient receptor potential channels (TRPs) and cannabinoid receptor type 1 (CB1) are two different types of Ca2+ permeation pathways that can be dysregulated during neoplasia. We determined in malignant human UM and healthy uvea and four different UM cell lines whether there is gene and functional expression of TRP subtypes and CB1 since they could serve as drug targets to either prevent or inhibit initiation and progression of UM. RT-PCR, Ca2+ transients, immunohistochemistry and planar patch-clamp analysis probed for their gene expression and functional activity, respectively. In UM cells, TRPV1 and TRPM8 gene expression was identified. Capsaicin (CAP), menthol or icilin induced Ca2+ transients as well as changes in ion current behavior characteristic of TRPV1 and TRPM8 expression. Such effects were blocked with either La3+, capsazepine (CPZ) or BCTC. TRPA1 and CB1 are highly expressed in human uvea, but TRPA1 is not expressed in all UM cell lines. In UM cells, the CB1 agonist, WIN 55,212-2, induced Ca2+ transients, which were suppressed by La3+ and CPZ whereas CAP-induced Ca2+ transients could also be suppressed by CB1 activation. Identification of functional TRPV1, TRPM8, TRPA1 and CB1 expression in these tissues may provide novel drug targets for treatment of this aggressive neoplastic disease.

Distinct Ca2+ channels maintain a high motility state of the sperm that may be needed for penetration of egg jelly of the newt, Cynops pyrrhogaster

Activation state of sperm motility named "hyperactivation" enables mammalian sperm to progress through the oviductal matrix, although a similar state of sperm motility is unknown in non-mammalian vertebrates at fertilization. Here, we found a high motility state of the sperm in the newt Cynops pyrrhogaster. It was predominantly caused in egg jelly extract (JE) and characterized by a high wave velocity of the undulating membrane (UM) that was significantly higher at the posterior midpiece. An insemination assay suggested that the high motility state might be needed for sperm to penetrate the egg jelly, which is the accumulated oviductal matrix. Specific characteristics of the high motility state were completely abrogated by a high concentration of verapamil, which blocks the L-type and T-type voltage-dependent Ca(2+) channels (VDCCs). Mibefradil, a dominant blocker of T-type VDCCs, suppressed the wave of the UM at the posterior midpiece with separate wave propagation from both the anterior midpiece and the posterior principal piece. In addition, nitrendipine, a dominant L-type VDCC blocker, weakened the wave of the UM, especially in the anterior midpiece. Live Ca(2+) imaging showed that, compared with the intact sperm in the JE, the relative intracellular Ca(2+) level changed especially in the anterior and posterior ends of the midpiece of the blocker-treated sperm. These suggest that different types of Ca(2+) channels mediate the intracellular Ca(2+) level predominantly in the anterior and posterior ends of the midpiece to maintain the high motility state of the newt sperm.

Kainate-induced calcium overload of cortical neurons in vitro: Dependence on expression of AMPAR GluA2-subunit and down-regulation by subnanomolar ouabain

Whereas kainate (KA)-induced neurodegeneration has been intensively investigated, the contribution of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) in neuronal Ca2+ overload ([Ca2+]i) is still controversial. Using Ca2+ imaging and patch-clamp techniques, we found different types of Ca2+ entry in cultured rat cortical neurons. The presence of Ca2+ in the extracellular solution was required to generate the [Ca2+]i responses to 30μM N-methyl-d-aspartate (NMDA) or KA. The dynamics of NMDA-induced [Ca2+]i responses were fast, while KA-induced responses developed slower reaching high [Ca2+]i. Ifenprodil, a specific inhibitor of the GluN2B subunit of NMDARs, reduced NMDA-induced [Ca2+]i responses suggesting expression of GluN1/GluN2B receptors. Using IEM-1460, a selective blocker of Ca2+-permeable GluA2-subunit lacking AMPARs, we found three neuronal responses to KA: (i) IEM-1460 resistant neurons which are similar to pyramidal neurons expressing Ca2+-impermeable GluA2-rich AMPARs; (ii) Neurons exhibiting nearly complete block of both KA-induced currents and [Ca2+]i signals by IEM-1460 may represent interneurons expressing GluA2-lacking AMPARs and (iii) neurons with moderate sensitivity to IEM-1460. Ouabain at 1nM prevented the neuronal Ca2+ overload induced by KA. The data suggest, that cultured rat cortical neurons maintain functional phenotypes of the adult brain cortex, and demonstrate the key contribution of the Na/K-ATPase in neuroprotection against KA excitotoxicity.

BIFURCATIONS AND CONTINUOUS TRANSITIONS IN A NONLINEAR MODEL OF INTRACELLULAR CALCIUM OSCILLATIONS

Oscillatory patterns in a one-pool model with Ca 2+-activated IP 3 degradation are presented and classified, based on fast/slow dynamical analysis and two-parameter bifurcations. The whole parameter space can be partitioned into two parts, that is, the oscillatory and rest regions. For this purpose, we perform the continuation of fold bifurcation, Hopf bifurcation and saddle-node bifurcation of limit cycles, respectively. Several distinct topological types of complex intracellular Ca 2+ oscillations (especially bursting) are investigated in the oscillatory area. The classification and transition of different types of Ca 2+ oscillations may offer a possible explanation for the differences in dynamic behavior observed in real cells in response to different levels of stimulation.

Modeling the contributions of Ca2+ flows to spontaneous Ca2+ oscillations and cortical spreading depression-triggered Ca2+ waves in astrocyte networks.

Astrocytes participate in brain functions through Ca2+ signals, including Ca2+ waves and Ca2+ oscillations. Currently the mechanisms of Ca2+ signals in astrocytes are not fully clear. Here, we present a computational model to specify the relative contributions of different Ca2+ flows between the extracellular space, the cytoplasm and the endoplasmic reticulum of astrocytes to the generation of spontaneous Ca2+ oscillations (CASs) and cortical spreading depression (CSD)-triggered Ca2+ waves (CSDCWs) in a one-dimensional astrocyte network. This model shows that CASs depend primarily on Ca2+ released from internal stores of astrocytes, and CSDCWs depend mainly on voltage-gated Ca2+ influx. It predicts that voltage-gated Ca2+ influx is able to generate Ca2+ waves during the process of CSD even after depleting internal Ca2+ stores. Furthermore, the model investigates the interactions between CASs and CSDCWs and shows that the pass of CSDCWs suppresses CASs, whereas CASs do not prevent the generation of CSDCWs. This work quantitatively analyzes the generation of astrocytic Ca2+ signals and indicates different mechanisms underlying CSDCWs and non-CSDCWs. Research on the different types of Ca2+ signals might help to understand the ways by which astrocytes participate in information processing in brain functions.

Intracellular Ca2+ Signalling and Phenotype of Vascular Smooth Muscle Cells

Vascular smooth muscle cells (VSMCs) express considerable plasticity in their phenotype and even can change their phenotype in vivo depending on the functional demand. In addition to contractile phenotype, VSMCs can be proliferative, migrating and/or synthetic. Importantly, contractile and non-contractile phenotypes differ significantly in their intracellular Ca²⁺ signalling, which is a consequence of difference in expression of Ca²⁺ transport proteins. Contractile VSMCs express Ca²⁺ transporters, including voltage-gated L-type Ca²⁺ channels and SERCA2a pump, which maintain low resting cytosolic Ca²⁺ and allow dynamic changes of Ca²⁺ in the spatial and temporal domain, while non-contractile VSMCs have significantly reduced voltage dependence of Ca²⁺ entry. These changes associated with phenotypic switch are consequences of changes in gene expression programmes, where the expression of phenotype-specific proteins and other proteins is suppressed. Importantly, Ca²⁺ -sensitive transcription factors, including serum response factor, cAMP response element-binding protein and nuclear factor of activated T lymphocytes, which are important for this phenotype switch, can be activated by different types of Ca²⁺ signalling. Thus, different Ca²⁺ transport proteins not only control averaged intracellular Ca²⁺ but also through their differences in the character of the Ca²⁺ signal modulate the activity of transcription factors and thus initiate phenotype switch. The essential stimuli for phenotype switch are unknown, but intracellular Ca²⁺ is an important second messenger in the cell transcription programme. This article reviews the relationship between intracellular Ca²⁺ signalling and VSMC phenotype.