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Results for “Calcium Signaling”

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At least 919 records · Page 51Linked to original sources
PubMed2001

Calcium signalling through nucleotide receptor P2X1 in rat portal vein myocytes.

1. ATP-mediated Ca2+ signalling was studied in freshly isolated rat portal vein myocytes by means of a laser confocal microscope and the patch-clamp technique. 2. In vascular myocytes held at -60 mV, ATP induced a large inward current that was supported mainly by activation of P2X1 receptors, although other P2X receptor subtypes (P2X3, P2X4 and P2X5) were revealed by reverse transcription-polymerase chain reaction. 3. Confocal Ca2+ measurements revealed that ATP-mediated Ca2+ responses started at initiation sites where spontaneous or triggered Ca2+ sparks were not detected, whereas membrane depolarizations triggered Ca2+ waves by repetitive activation of Ca2+ sparks from a single initiation site. 4. ATP-mediated Ca2+ responses depended on Ca2+ influx through non-selective cation channels that activated, in turn, Ca2+ release from the intracellular store via ryanodine receptors (RYRs). Using specific antibodies directed against the RYR subtypes, we show that ATP-mediated Ca2+ release requires, at least, RYR2, but not RYR3. 5. Our results suggest that, in vascular myocytes, Ca2+ influx through P2X1 receptors may trigger Ca2+-induced Ca2+ release at intracellular sites where RYRs are not clustered.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed2006

Calcium signaling phenomena in heart diseases: a perspective.

Ca(2+) is a major intracellular messenger and nature has evolved multiple mechanisms to regulate free intracellular (Ca(2+))(i) level in situ. The Ca(2+) signal inducing contraction in cardiac muscle originates from two sources. Ca(2+) enters the cell through voltage dependent Ca(2+) channels. This Ca(2+) binds to and activates Ca(2+) release channels (ryanodine receptors) of the sarcoplasmic reticulum (SR) through a Ca(2+) induced Ca(2+) release (CICR) process. Entry of Ca(2+) with each contraction requires an equal amount of Ca(2+) extrusion within a single heartbeat to maintain Ca(2+) homeostasis and to ensure relaxation. Cardiac Ca(2+) extrusion mechanisms are mainly contributed by Na(+)/Ca(2+) exchanger and ATP dependent Ca(2+) pump (Ca(2+)-ATPase). These transport systems are important determinants of (Ca(2+))(i) level and cardiac contractility. Altered intracellular Ca(2+) handling importantly contributes to impaired contractility in heart failure. Chronic hyperactivity of the beta-adrenergic signaling pathway results in PKA-hyperphosphorylation of the cardiac RyR/intracellular Ca(2+) release channels. Numerous signaling molecules have been implicated in the development of hypertrophy and failure, including the beta-adrenergic receptor, protein kinase C, Gq, and the down stream effectors such as mitogen activated protein kinases pathways, and the Ca(2+) regulated phosphatase calcineurin. A number of signaling pathways have now been identified that may be key regulators of changes in myocardial structure and function in response to mutations in structural components of the cardiomyocytes. Myocardial structure and signal transduction are now merging into a common field of research that will lead to a more complete understanding of the molecular mechanisms that underlie heart diseases. Recent progress in molecular cardiology makes it possible to envision a new therapeutic approach to heart failure (HF), targeting key molecules involved in intracellular Ca(2+) handling such as RyR, SERCA2a, and PLN. Controlling these molecular functions by different agents have been found to be beneficial in some experimental conditions.

Animals↗
PubMed2003

Oxidative stress and calcium signaling in the adverse effects of environmental particles (PM10).

This review focuses on the potential role that oxidative stress plays in the adverse effects of PM(10). The central hypothesis is that the ability of PM(10) to cause oxidative stress underlies the association between increased exposure to PM(10) and both exacerbations of lung disease and lung cancer. Pulmonary inflammation may also underlie the cardiovascular effects seen following increased PM(10), although the mechanisms of the cardiovascular effects of PM(10) are not well understood. PM(10) is a complex mix of various particle types and several of the components of PM(10) are likely to be involved in the induction of oxidative stress. The most likely of these are transition metals, ultrafine particle surfaces, and organic compounds. In support of this hypothesis, oxidative stress arising from PM(10) has been shown to activate a number of redox-responsive signaling pathways in lung target cells. These pathways are involved in expression of genes that play a role in responses relevant to inflammation and pathological change, including MAPKs, NF-kappaB, AP-1, and histone acetylation. Oxidative stress from particles is also likely to play an important role in the carcinogenic effects associated with PM(10) and hydroxyl radicals from PM(10) cause DNA damage in vitro.

Animals↗
PubMed2002

Acetylcholine-induced calcium signaling and contraction of airway smooth muscle cells in lung slices.

The Ca(2+) signaling and contractility of airway smooth muscle cells (SMCs) were investigated with confocal microscopy in murine lung slices (approximately 75-microm thick) that maintained the in situ organization of the airways and the contractility of the SMCs for at least 5 d. 10--500 nM acetylcholine (ACH) induced a contraction of the airway lumen and a transient increase in [Ca(2+)](i) in individual SMCs that subsequently declined to initiate multiple intracellular Ca(2+) oscillations. These Ca(2+) oscillations spread as Ca(2+) waves through the SMCs at approximately 48 microm/s. The magnitude of the airway contraction, the initial Ca(2+) transient, and the frequency of the subsequent Ca(2+) oscillations were all concentration-dependent. In a Ca(2+)-free solution, ACH induced a similar Ca(2+) response, except that the Ca(2+) oscillations ceased after 1--1.5 min. Incubation with thapsigargin, xestospongin, or ryanodine inhibited the ACH-induced Ca(2+) signaling. A comparison of airway contraction with the ACH-induced Ca(2+) response of the SMCs revealed that the onset of airway contraction correlated with the initial Ca(2+) transient, and that sustained airway contraction correlated with the occurrence of the Ca(2+) oscillations. Buffering intracellular Ca(2+) with BAPTA prohibited Ca(2+) signaling and airway contraction, indicating a Ca(2+)-dependent pathway. Cessation of the Ca(2+) oscillations, induced by ACH-esterase, halothane, or the absence of extracellular Ca(2+) resulted in a relaxation of the airway. The concentration dependence of the airway contraction matched the concentration dependence of the increased frequency of the Ca(2+) oscillations. These results indicate that Ca(2+) oscillations, induced by ACH in murine bronchial SMCs, are generated by Ca(2+) release from the SR involving IP(3)- and ryanodine receptors, and are required to maintain airway contraction.

Acetylcholine↗
PubMed2003

Calcium signaling and apoptosis.

Ca(2+) is one of the key regulators of cell survival, but Ca(2+) can also induce apoptosis in response to a variety of pathological conditions. The pro-apoptotic effects of Ca(2+) are mediated by a diverse range of Ca(2+)-sensitive factors that are compartmentalized in various intracellular organelles including the ER, cytoplasm, and mitochondria. The Ca(2+) dynamics of these organelles appear to be modulated by the apoptosis-regulating Bcl-2 family proteins. In this paper, the recent progress of research on the mechanisms mediating the apoptosis-regulating effects of Ca(2+) and the interactions of Bcl-2 family proteins with the Ca(2+) storage organelles are discussed.

Animals↗
PubMed2004

Quantitative investigation of calcium signals for locomotor pattern generation in the lamprey spinal cord.

Locomotor pattern generation requires the network coordination of spinal ventral horn neurons acting in concert with the oscillatory properties of individual neurons. In the spinal cord, N-methyl-d-aspartate (NMDA) activates neuronal oscillators that are believed to rely on Ca(2+) entry to the cytosol through voltage-operated Ca(2+) channels and synaptically activated NMDA receptors. Ca(2+) signaling in lamprey ventral horn neurons thus plays a determinant role in the regulation of the intrinsic membrane properties and network synaptic interaction generating spinal locomotor neural pattern activity. We have characterized aspects of this signaling quantitatively for the first time. Resting Ca(2+) concentrations were between 87 and 120 nM. Ca(2+) concentration measured during fictive locomotion increased from soma to distal dendrites [from 208 +/- 27 (SE) nM in the soma to 335 +/- 41 nM in the proximal dendrites to 457 +/- 68 nM in the distal dendrites]. We sought to determine the temporal and spatial properties of Ca(2+) oscillations, imaged with Ca(2+)-sensitive dyes and correlated with fluctuations in membrane potential, during lamprey fictive locomotion. The Ca(2+) signals recorded in the dendrites showed a great deal of spatial heterogeneity. Rapid changes in Ca(2+)-induced fluorescence coincided with action potentials, which initiated significant Ca(2+) transients distributed throughout the neurons. Ca(2+) entry to the cytosol coincided with the depolarizing phase of the locomotor rhythm. During fictive locomotion, larger Ca(2+) oscillations were recorded in dendrites compared with somata in motoneurons and premotor interneurons. Ca(2+) fluctuations were barely detected with dyes of lower affinity providing alternative empirical evidence that Ca(2+) responses are limited to hundreds of nanomolars during fictive locomotion.

Action Potentials↗
PubMed2005

Evidence for downregulation of calcium signaling proteins in advanced mouse adenocarcinoma.

BACKGROUND: Prostate cancer (PCa) is the leading cancer related death in America. Gleason grading is currently the predominant method for prediction, with only few biomarkers available. More biomarkers, especially as they relate to cancer progression are desirable. METHODS: The abundance of several important proteins in prostate tissue was compared between wild-type mouse dorsal prostate and well-differentiated transgenic adenocarcinoma mouse prostate (TRAMP) mouse dorsal prostates, and between wild-type mouse dorsal prostate and poorly-differentiated TRAMP mouse tumor tissue. 2DIGE method in conjunction with MALDI-ToF and Western blots was used to determine differential expression. RESULTS: In TRAMP dorsal prostates with well-differentiated adenocarcinoma, there were few significant changes in the protein abundances compared to wild-type dorsal prostates, with the exception of increases in proliferating cell nuclear antigen (PCNA) and beta tubulin, two proteins implicated in cell proliferation, and a more than 2-fold increase in Hsp60, a protein involved in the suppression of apoptosis. In the poorly-differentiated tumors, the changes in protein abundance were substantial. While some of those changes could be related to the disappearance of stromal tissue or the appearance of epithelial tissue, other changes in protein abundance were more significant to the cancer development itself. Most notable was the overall decrease in calcium homeostasis proteins with a 10-fold decrease in calreticulin and Hsp70 and a 40-fold decrease in creatine kinase bb in the cancerous tissue. CONCLUSIONS: Proteomics of TRAMP mice provide an excellent method to observe changes in protein abundance, revealing changes in pathways during cancer progression.

Adenocarcinoma↗
PubMed2004

2-APB inhibits volume-regulated anion channels independently from intracellular calcium signaling modulation.

It has previously been suggested that volume-regulated anion channels (VRACs) and store-operated channels (SOCs) interact with each other according to their expected colocalization in the plasma membrane of LNCaP cells. In order to study interactions between these two channels, we used 2-aminoethoxydiphenyl borate (2-APB) as a regular SOC inhibitor. Surprisingly 2-APB reduced VRAC activity in a dose-dependent manner (IC(50)=122.8 microM), but not 2,2-diphenyltetrahydrofuran (a structural analog of 2-APB). This effect was also present in keratinocytes. We conclude that 2-APB is an inhibitor of the VRAC family, and is also a potent tool to study the SOC-VRAC interaction in LNCaP cells.

Boron Compounds↗
PubMed2006

Calcium signaling pathways mediating synaptic potentiation triggered by amyotrophic lateral sclerosis IgG in motor nerve terminals.

Sporadic amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects particularly motoneurons. Several pieces of evidence suggested the involvement of autoimmune mechanisms mediated by antibodies in ALS. However, the significance of those antibodies in the disease and the underlying mechanisms are unknown. Here we showed that IgG purified from a group of sporadic ALS patients, but not familial ALS patients, specifically interact with the presynaptic membrane of motoneurons through an antigen-antibody interaction and modulated synaptic transmission. Immunoreactivity against nerve terminals showed strong correlation with synaptic modulation ability. In addition, several controls have ruled out the possibility for this synaptic modulation to be mediated through proteases or nonspecific effects. Effective IgG potentiated both spontaneous and asynchronous transmitter release. Application of pharmacological inhibitors suggested that activation of this increased release required a nonconstitutive Ca2+ influx through N-type (Cav2.2) channels and phospholipase C activity and that activation of IP3 and ryanodine receptors were necessary to both activate and sustain the increased release. Consistent with the notion that ALS is heterogeneous disorder, our results reveal that, in approximately 50% of ALS patients, motor nerve terminals constitutes a target for autoimmune response.

Adult↗
PubMed2000

Calcium signalling in sarcoplasmic reticulum, cytoplasm and mitochondria during activation of rabbit aorta myocytes.

This study investigated the relationship between cytoplasmic, mitochondrial, and sarcoplasmic reticulum (SR) [Ca(2+)] in rabbit aorta smooth muscle cells, following cell activation. Smooth muscle cells were loaded with the Ca(2+)-sensitive fluorescent indicator Mag-Fura-2-AM, and then either permeabilized by exposure to saponin, or dialyzed with a patch pipette in the whole-cell configuration to remove cytoplasmic indicator. When the intracellular solution contained millimolar EGTA or BAPTA, activation of SR Ca(2+)release through IP(3)or ryanodine receptors induced a decrease in the [Ca(2+)] reported by Mag-Fura-2. However, when EGTA was present at < or =100 microM, the same stimuli caused an increase in the [Ca(2+)] reported by Mag-Fura-2. The increase in [Ca(2+)] caused by phenylephrine or caffeine was delayed, and prolonged, with respect to the cytoplasmic Ca(2+)transient. Evidence is presented that this Mag-Fura-2 signal reflected a rise in mitochondrial [Ca(2+)]. Agents that inhibit mitochondrial function, such as FCCP or cyanide in combination with oligomycin B, converted the increase in organelle Mag-Fura-2 fluorescence to a decrease, while also prolonging the cytoplasmic Ca(2+)transient. There was considerable similarity between the localization of Mag-Fura-2 fluorescence and the mitochondria-selective indicator tetramethylrhodamine ethyl ester. Thus, we propose that there is close functional integration between the SR and mitochondria in aorta smooth muscle cells, with mitochondria taking up Ca(2+)from the cytoplasm following cell activation.

Animals↗
PubMed2001

Return of potassium ion channels in regenerated hair cells: possible pathways and the role of intracellular calcium signaling.

Recent electrophysiological studies in pigeon have demonstrated that potassium channels are completely functional in regenerated type II hair cells at 21 days post-treatment (PT) with ototoxic doses of streptomycin. The currents return in the order they appear during development. The mixture of ionic currents in a regenerated type II hair cell in a particular region of the neuroepithelium is the same as in its ancestor in that region. The return of currents in regenerated type I hair cells is more complicated. The dominant conductance gKI is not present until after 70 days PT. Before 70 days, the ionic currents in type I hair cells resemble those of regenerated type II hair cells, suggesting that the ionic currents in type II hair cells might be precursors of the ionic currents in regenerated type I hair cells. New data show that at one year PT, the kinetics and drug sensitivity of the dominant K+ conductance in type I hair cells are identical to gKI. Supporting cells, believed to be the precursors of regenerated type II hair cells, have effectively no voltage-gated outward potassium channels, suggesting that regenerated type II hair cells must develop these channels de novo. The next step is to understand the mechanisms by which the potassium channel protein is synthesized, migrates through the cytosol, and is inserted into the plasmalemma of regenerating hair cells. These mechanisms are unknown. We propose that intracellular calcium is involved in this process, as well as in the differentiation, proliferation, and gene regulation of precursor cells fated to become hair cells.

Animals↗
PubMed2005

Phospholipase C-gamma: diverse roles in receptor-mediated calcium signaling.

Ca2+ is a universal signal: the dynamic changes in its release and entry trigger a plethora of cellular responses. Central to this schema are members of the phospholipase C (PLC) superfamily, which relay information from the activated receptor to downstream signal cascades by production of second-messenger molecules. Recent studies reveal that, in addition to its enzymatic activity, PLC-gamma regulates Ca2+ entry via the formation of an intermolecular lipid-binding domain with canonical transient receptor potential 3 (TRPC3) ion channels. This complex, in turn, controls TRPC3 trafficking and cell-surface expression. Thus, TRPC3 ion channels are functionally linked to both lipase-dependent and -independent activities of PLC-gamma. Understanding the underlying molecular mechanisms that regulate this complex will probably clarify the processes of receptor-activated Ca2+ entry.

Amino Acid Sequence↗
PubMedDate not supplied

Calcium signaling in liver.

In hepatocytes, hormones linked to the formation of the second messenger inositol 1,4,5-trisphosphate (InsP3) evoke transient increases or spikes in cytosolic free calcium ([Ca2+]i), that increase in frequency with the agonist concentration. These oscillatory Ca2+ signals are thought to transmit the information encoded in the extracellular stimulus to down-stream Ca2+-sensitive metabolic processes. We have utilized both confocal and wide field fluorescence microscopy techniques to study the InsP3-dependent signaling pathway at the cellular and subcellular levels in the intact perfused liver. Typically InsP3-dependent [Ca2+]i spikes manifest as Ca2+ waves that propagate throughout the entire cytoplasm and nucleus, and in the intact liver these [Ca2+]i increases are conveyed through gap junctions to encompass entire lobular units. The translobular movement of Ca2+ provides a means to coordinate the function of metabolic zones of the lobule and thus, liver function. In this article, we describe the characteristics of agonist-evoked [Ca2+]i signals in the liver and discuss possible mechanisms to explain the propagation of intercellular Ca2+ waves in the intact organ.

Animals↗
PubMed2007

Regulation of calcium signalling by adenine-based second messengers.

cADPR [cyclic ADPR (ADP-ribose)], NAADP (nicotinic acid-adenine dinucleotide phosphate) and ADPR belong to the family of adenine-containing second messengers. They are metabolically related and are all involved in the regulation of cellular Ca(2+) homoeostasis. Activation of specific plasma membrane receptors is connected to cADPR formation in many cell types and tissues. In contrast receptor-mediated formation of NAADP and ADPR has been shown only in a few selected cellular systems. The intracellular Ca(2+) channel triggered by cADPR is the RyR (ryanodine receptor); in the case of NAADP, both activation of RyR and a novel Ca(2+) channel have been proposed. In contrast, ADPR opens the non-specific cation channel TRPM2 [TRP (transient receptor potential) melastatin 2] that belongs to the TRP family of ion channels.

Adenine↗
PubMed1999

Calcium signals in cell lines derived from the cerebral cortex of normal and trisomy 16 mice.

We established two immortalized cell lines from cerebral cortex of normal (CNh) and trisomy 16 (CTb) mouse fetuses, an animal model of human trisomy 21. Those cells loaded with the fluorescent Ca2+ dyes, Indo-1 and Fluo-3, exhibited increments of intracellular Ca2+ ([Ca2+]i) in response to external glutamate, NMDA, AMPA and kainate. CTb cells exhibited higher basal Ca2+ concentrations and had higher amplitude and slower time-dependent kinetics in the decay than CNh cells, suggesting an impaired Ca2+ buffering capacity in the trisomy 16-derived cell line. Nicotine also induced increments of [Ca2+]i. The CTb cell line could represent a model for studying cellular alterations related to Down syndrome.

Animals↗
PubMed2000

Calcium signals in prostate cancer cells: specific activation by bone-matrix proteins.

Cancer of the prostate commonly metastasizes to bony sites where cells acquire an aggressive, rapidly proliferating, androgen-independent phenotype. The interaction between bone and prostate, thus, becomes a key factor in disease progression. Fluctuations in intracellular ionized Ca2+ [Ca2+]i are rapid, regulated signal transduction events often associated with cell proliferation. Hence, Ca2+ signals provide a convenient measure of early events in cancer cell growth. This study developed single cell fluorescent imaging techniques to visualize Ca2+ signals in Fura-2 loaded prostatic cancer cell lines of various metastatic phenotypes. Solubilized bone fractions containing extracellular matrix and associated proteins were tested for the ability to trigger Ca2+ signals in prostate cancer cell lines. Fractions representing the complete repertoire of non-collagenous proteins present in mineralized bone were tested. Results demonstrated that two bone fractions termed D3b- and D4a-triggered Ca2+ signals in prostate cancer cells derived from bone (PC-3), but not brain (DU-145) metastases of prostate cancer. Lymph-node derived LNCaP cells also did not produce a Ca2+ signal in response to addition of soluble bone matrix. No other bone fractions produced a Ca2+ signal in PC-3 cells. It is of interest that bone fractions D3b and D4a contain a number of non-collagenous matrix proteins including osteonectin (SPARC) and osteopontin (OPN), as well as prothrombin. Moreover, antibody LM609 that recognizes the alpha v beta 3 integrin, blocks the ability of OPN to trigger a Ca2+ transient in PC-3 cells. These studies support a conclusion that bone-matrix proteins play a role in the growth and progression of metastatic prostate cancer, and that prior growth in bone may be associated with development of a bone-matrix-responsive phenotype.

Adenosine Triphosphate↗
PubMedDate not supplied

Calcium signalling in squid olfactory receptor neurons.

Isolated squid olfactory receptor neurons respond to dopamine and betaine with hyperpolarizing conductances. We used Ca(2+) imaging techniques to determine if changes in intracellular Ca(2+) were involved in transducing the hyperpolarizing odor responses. We found that dopamine activated release of Ca(2+) from intracellular stores while betaine did not change internal Ca(2+) concentrations. Application of 10 mM caffeine also released Ca(2+) from intracellular stores, suggesting the presence of ryanodine-like receptors. Depletion of intracellular stores with 100 microM thapsigargin revealed the presence of a Ca(2+) store depletion-activated Ca(2+) influx. The influx of Ca(2+) through the store-operated channel was reversibly blocked by 10 mM Cd(2+). Taken together, these data suggest a novel odor transduction system in squid olfactory receptor neurons involving Ca(2+) release from intracellular stores.

Animals↗