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Results for “Calcium Signaling”

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At least 865 records · Page 48Linked to original sources
PubMed2006

Cannabinoid receptor-mediated inhibition of calcium signaling in rat retinal ganglion cells.

PURPOSE: The physiological actions of CB(1) cannabinoid receptors (CB(1)Rs) in mammalian retina have yet to be fully described in all cell types. Here we investigate the actions of CB(1)R activation on high-voltage-activated (HVA) Ca(2+) channel currents in purified cultures of rat retinal ganglion cells (RGCs). METHODS: Reverse transcriptase polymerase chain reaction (RT-PCR) and immunocytochemistry were used to determine the presence of CB(1)R mRNA and protein in a purified RGC culture generated from neonatal rats using a two-step panning procedure. Ruptured-patch whole-cell voltage clamp was used to test the effect of CB(1)R agonists (WIN 55,212-2) and antagonists (SR141716A, AM281) on HVA Ca(2+) channel currents. RESULTS: RT-PCR analysis confirmed CB(1)R mRNA in cultured RGCs and immunocytochemistry for CB(1)R protein revealed labeling in both the cell body and neurites of isolated RGCs. Patch-clamp recording from cultured rat RGCs showed that the CB(1)R agonist WIN 55,212-2 inhibited HVA Ca(2+) channel currents up to 50% in a concentration-dependent manner (0.5, 1, and 5 muM). The Ca(2+) channel current inhibition by WIN 55,212-2 was blocked by CB(1)R antagonists AM281 and SR141716. CONCLUSIONS: Activation of CB(1)Rs in cultured RGCs inhibits HVA Ca(2+) channel currents. These data show that cannabinoids can modify the excitability of RGCs and could affect retinal output. This finding has implications for retinal signal processing as it suggests that endogenous cannabinoids have inhibitory effects on RGCs and that exogenous cannabinoids could modulate retinal function by this pathway as well.

Animals↗
PubMed1998

Dual action of androgen on calcium signaling and luteinizing hormone secretion in pituitary gonadotrophs.

An increase in serum androgen levels associated with a suppression of cyclic gonadotropin secretion is frequently observed in females with impaired ovarian function. Here, we addressed the hypotheses that androgens (testosterone and dihydrotestosterone) alter gonadotropin secretion by modulating agonist-induced Ca2+ signaling and/or Ca(2+)-controlled exocytosis. In mixed populations of pituitary cells from female rats, addition of testosterone reduced basal and agonist (GnRH)-induced gonadotropin secretion in a concentration- and time-dependent manner. The suppressive actions of this androgen on gonadotropin secretion were observed over the full GnRH concentration range. Reduction in agonist-induced gonadotropin secretion was also observed after addition of dihydrotestosterone, indicating that the inhibitory action of testosterone is not mediated by its conversion to estradiol. Both the extracellular Ca(2+)-independent spike phase and extracellular Ca(2+)-dependent sustained phase of GnRH-induced gonadotropin secretions were affected by testosterone. In part, the inhibitory action of testosterone was mediated by attenuation of GnRH-induced InsP3 production and InsP3-dependent Ca2+ mobilization. In addition, testosterone exhibited a Ca(2+)-independent action on gonadotropin secretion, as documented by attenuation of high potassium-induced secretion without an affect on depolarization-induced Ca2+ signals. These results suggest that androgen inhibition of gonadotropin secretion occurs at two distinct steps in the secretory pathway, one prior to and one after elevation in cytosolic Ca2+ concentration.

Androgens↗
PubMed2004

Calcium signaling in chemorepellant Slit2-dependent regulation of neuronal migration.

Migration of neuronal precursor cells in the developing brain is guided by extracellular cues, but intracellular signaling processes underlying the guidance of neuronal migration are largely unknown. By examining the migration of cerebellar granule neurons along the surface of cocultured astroglial cells, we found that an extracellular gradient of Slit2, a chemorepellant for neuronal migration in vivo, caused a reversal in the direction of migration without affecting the migration speed. A Slit2 gradient elevated the intracellular concentration of Ca2+, probably due to calcium release from the internal store, led to a reversal of the preexisting asymmetric intracellular Ca2+ distribution in the soma of migrating neurons, and this reversal was closely related with its action of reversing the migrating direction. Asymmetric Ca2+ distribution in the soma was both necessary and sufficient for directing neuronal migration. These results have demonstrated an important role for Ca2+ in mediating neuronal responses to Slit2 and suggest a general mechanism for neuronal guidance.

Animals↗
PubMed2005

Effects of the prostaglandins PGF2alpha and PGE2 on calcium signaling in rat hepatocyte doublets.

Coordination of intercellular Ca2+ signals is important for certain hepatic functions including biliary flow and glucose output. Prostaglandins, such as PGF2alpha and PGE2, may modify these hepatocyte functions by inducing Ca2+ increase, but very little is known about the organization of the Ca2+ signals induced by these agonists. We studied Ca2+ signals induced by PGF2alpha and PGE2 in fura-2 AM-loaded hepatocyte doublets. Even though both prostaglandins induced Ca2+ oscillations, neither PGF2alpha nor PGE2 induced coordinated Ca2+ oscillations in hepatocyte doublets. Gap junction permeability (GJP), assessed by fluorescence recovery after photobleaching, showed that this absence of coordination was not related to a defect in GJP. Inositol (1,4,5)trisphosphate [Ins(1,4,5)P3] assays and the increase in Ins(1,4,5)P3 receptor sensitivity to Ins(1,4,5)P3 observed in response to thimerosal suggested that the absence of coordination was a consequence of the very small quantity of Ins(1,4,5)P3 formed by these prostaglandins. Furthermore, when PGE2 and PGF2alpha were added just before norepinephrine, they favored the coordination of Ca2+ signals induced by norepinephrine. However, GJP between hepatocyte doublets was strongly inhibited by prolonged (>or=2 h) treatment with PGF2alpha, thereby preventing the coordination of Ca2+ oscillations induced by norepinephrine in these cells. Thus, depending on the time window, prostaglandins, specially PGF2alpha, may enhance or diminish the propagation of Ca2+ signals. They may therefore contribute to the fine tuning of Ca2+ wave-dependent functions, such as nerve stimulation, hormonal regulation of liver metabolism, or bile secretion, in both normal and pathogenic conditions.

Animals↗
PubMed2004

IGF-I and insulin induce different intracellular calcium signals in skeletal muscle cells.

We studied the effect of IGF-I and insulin on intracellular Ca(2+) in primary cultured myotubes. IGF-I induced a fast and transient Ca(2+) increase, measured as fluo-3 fluorescence. This response was blocked by both genistein and AG538. IGF-I induced a fast inositol-1,4,5-trisphosphate (IP(3)) increase, kinetically similar to the Ca(2+) rise. The Ca(2+) signal was blocked by inhibitors of the IP(3) pathway. On the other hand, insulin produced a fast (<1 s) and transient Ca(2+) increase. Insulin-induced Ca(2+) increase was blocked in Ca(2+)-free medium and by either nifedipine or ryanodine. In the normal muscle NLT cell line, the Ca(2+ )signals induced by both hormones resemble those of primary myotubes. GLT cells, lacking the alpha1-subunit of dihydropyridine receptor (DHPR), responded to IGF-I but not to insulin, while GLT cells transfected with the alpha1-subunit of DHPR reacted to both hormones. Moreover, dyspedic muscle cells, lacking ryanodine receptors, responded to IGF-I as NLT cells, however they show no insulin-induced calcium increase. Moreover, G-protein inhibitors, pertussis toxin (PTX) and GDPbetaS, blocked the insulin-induced Ca(2+) increase without major modification of the response to IGF-I. The different intracellular Ca(2+) patterns produced by IGF-I and insulin may improve our understanding of the early action mechanisms for these hormones in skeletal muscle cells.

Animals↗
PubMed2002

Cholecystokinin-8 induces intracellular calcium signaling in cultured myenteric neurons from neonatal guinea pigs.

The responsiveness of cultured myenteric neurons to cholecystokinin (CCK-8) was examined using fura-2-based digital microfluorimetric measurement of intracellular calcium ([Ca(2+)](i)). CCK-8 (10(-10)-10(-6)M) evoked concentration-dependent increases in percentage of neurons responding (8-52%) and delta[Ca(2+)](i) (76-169 nM). Gastrin (1 microM) also induced an increase in [Ca(2+)](i) in 29+/-6% of neurons (delta[Ca(2+)](i): 71+/-3 nM). L-364,718, an antagonist for the CCK-A receptor, blocked [Ca(2+)](i) response to CCK-8. Removal of extracellular calcium eliminated CCK-induced [Ca(2+)](i) increments, as did the addition of the calcium channel inhibitors nickel (1mM) and lanthanum (5mM). Nifedipine (1-50 microM) dose-dependently attenuated CCK-caused [Ca(2+)](i) responses. CCK evokes [Ca(2+)](i) signaling in myenteric neurons by the influx of extracellular calcium, likely through L-type calcium channels.

Animals↗
PubMed2005

Ca2+ blinks: rapid nanoscopic store calcium signaling.

Luminal Ca(2+) in the endoplasmic and sarcoplasmic reticulum (ER/SR) plays an important role in regulating vital biological processes, including store-operated capacitative Ca(2+) entry, Ca(2+)-induced Ca(2+) release, and ER/SR stress-mediated cell death. We report rapid and substantial decreases in luminal [Ca(2+)], called "Ca(2+) blinks," within nanometer-sized stores (the junctional cisternae of the SR) during elementary Ca(2+) release events in heart cells. Blinks mirror small local increases in cytoplasmic Ca(2+),orCa(2+) sparks, but changes of [Ca(2+)] in the connected free SR network were below detection. Store microanatomy suggests that diffusional strictures may account for this paradox. Surprisingly, the nadir of the store depletion trails the peak of the spark by about 10 ms, and the refilling of local store occurs with a rate constant of 35 s(-1), which is approximately 6-fold faster than the recovery of local Ca(2+) release after a spark. These data suggest that both local store depletion and some time-dependent inhibitory mechanism contribute to spark termination and refractoriness. Visualization of local store Ca(2+) signaling thus broadens our understanding of cardiac store Ca(2+) regulation and function and opens the possibility for local regulation of diverse store-dependent functions.

Animals↗
PubMed2002

Phthalates suppress the calcium signaling of nicotinic acetylcholine receptors in bovine adrenal chromaffin cells.

Researchers have recently reported on the nongenomic action of estrogen via membrane receptors and ion channels, especially nicotinic acetylcholine receptors (nAChR). We studied the nongenomic effects of eight phthalates (an endocrine disrupter that expresses estrogen-like activity through estrogen receptors): di-n-ethyl (DEP), di-n-propyl (DPrP), di-n-butyl (DBP), benzyl-n-butyl (BBP), di-n-pentyl (DPP), di-n-hexyl (DHP), dicyclohexyl (DCHP), and di-(2-ethylhexyl) (DEHP). Specifically, we looked at their individual effects on cytosolic free calcium concentration rise induced by three nAChR agonists: carbachol, 1,1-dimethyl-4-phenyl-piperazinium iodide, and epibatidine. Results show that all of the tested phthalates suppressed nAChR-coupled Ca(2+) response. Strongest to weakest potencies were observed as DPP --> BBP --> DBP --> DCHP --> DHP --> DPrP --> DEHP --> DEP. DPP, DBP, and BBP were 10 times more potent than estradiol. We suggest that phthalate potency was associated with its chemical structure, since (a) the most effective phthalates had dialkyl group carbon numbers of C4 or C5, with shorter or longer numbers resulting in decreased potency, and (b) the presence of an alkyl ring or phenoic structure resulted in increasing potency. Because of the similarity between this relationship and estrogen receptor-binding potency, we suggest that the inhibitory effect of phthalates on nAChR-coupled Ca(2+) response is an indication of their nongenomic estrogen-like activity.

Adrenal Medulla↗
PubMed2004

The chemokine CXCL10 modulates excitatory activity and intracellular calcium signaling in cultured hippocampal neurons.

In this study, we provide evidence for direct modulatory effects of the chemokine, CXCL10, on the physiology of hippocampal neurons maintained in primary culture. CXCL10 elicited a rise in intracellular Ca2+ and enhanced both spontaneous and evoked electrical activity of hippocampal neurons. CXCL10-induced elevations in intracellular Ca2+ were associated with an increase in neuronal firing and an alteration in the relationship between the evoked Ca2+ signal and neuronal activity. The effects of CXCL10 were not accompanied by a shift in resting membrane potential (RMP) or input resistance. Expression of the CXCR3 chemokine receptor supports a direct effect of CXCL10 on hippocampal neurons.

Action Potentials↗
PubMed2005

Calcium signaling in terminal Schwann cells associated with lanceolate sensory endings in rat vibrissae.

Transient elevations of the intracellular Ca2+ concentration ([Ca2+]i) in glia mediate various cell activities to regulate neuronal functions. The present study focuses on spatiotemporal dynamics of Ca2+ signaling in terminal Schwann cells, glial elements of the lanceolate sensory endings innervating the rat vibrissa. Arrays of lanceolate endings were enzymatically isolated from the vibrissal follicle, and subjected to [Ca2+]i image recording by time-lapse confocal microscopy. Each terminal Schwann cell displayed a round cell body, and extended long cytoplasmic stalks, which branched into two to five lamellae resting on different axon endings. Each axon ending, on the other hand, was covered on both flattened sides of the lancet by two Schwann lamellae of different cell origin. Thus the peripheral glia constituted an extensive network connecting the sensory endings. Image analyses of [Ca2+]i characterized the Schwann lamellae as functional compartments that can independently generate Ca2+ signals: these cell portions primarily responded to local mechanical stimuli with a [Ca2+]i spike, and individually initiated [Ca2+]i oscillations during bath application of the sensory modulator adenosine 5'-triphosphate (ATP). The stimulus-induced signals sometimes propagated along the glial network to activate neighboring lamellae after a delay of 2-4 sec. These findings suggest that the terminal Schwann cells contribute both to individual regulation and total coordination of the arrayed sensory endings.

Adenosine Triphosphate↗
PubMed2004

State-dependent calcium signaling in dendritic spines of striatal medium spiny neurons.

Striatal medium spiny neurons (MSNs) in vivo undergo large membrane depolarizations known as state transitions. Calcium (Ca) entry into MSNs triggers diverse downstream cellular processes. However, little is known about Ca signals in MSN dendrites and spines and how state transitions influence these signals. Here, we develop a novel approach, combining 2-photon Ca imaging and 2-photon glutamate uncaging, to examine how voltage-sensitive Ca channels (VSCCs) and ionotropic glutamate receptors contribute to Ca signals in MSNs. We find that upstate transitions switch the VSCCs available in dendrites and spines, decreasing T-type while enhancing L-type channels. Moreover, these transitions change the dominant synaptic Ca source from Ca-permeable AMPA receptors to NMDA receptors. Finally, pairing bAPs with synaptic inputs generates additional synaptic Ca signals due to enhanced Ca influx through NMDA receptors. By altering the sources, amplitude, and kinetics of spine Ca signals, state transitions may gate synaptic plasticity and gene expression in MSNs.

Animals↗
PubMed2006

Calcium signaling complexes in microdomains of polarized secretory cells.

The highly polarized nature of epithelial cells in exocrine glands necessitates targeting, assembly into complexes and confinement of the molecules comprising the Ca(2+) signaling apparatus, to cellular microdomains. Such high degree of polarized localization has been shown for all Ca(2+) signaling molecules tested, including G protein coupled receptors and their associated proteins, Ca(2+) pumps, Ca(2+) influx channels at the plasma membrane and Ca(2+) release channels in the endoplasmic reticulum. Although the physiological significance of polarized Ca(2+) signaling is clear, little is known about the mechanism of targeting, assembly and retention of Ca(2+) signaling complexes in cellular microdomains. The present review attempts to summarize the evidence in favor of polarized expression of Ca(2+) signaling proteins at the apical pole of secretory cells with emphasis on the role of scaffolding proteins in the assembly and function of the Ca(2+) signaling complexes. The consequence of polarized enrichment of Ca(2+) signaling complexes at the apical pole is generation of an apical to basal pole gradient of cell responsiveness that, at low physiological agonist concentrations, limits Ca(2+) spikes to the apical pole, and when a Ca(2+) wave occurs, it always propagates from the apical to the basal pole. Our understanding of Ca(2+) signaling in microdomains is likely to increase rapidly with the application of techniques to controllably and selectively disrupt components of the complexes and apply high resolution recording techniques, such as TIRF microscopy to this problem.

Animals↗
PubMed2000

Multiple types of calcium signals are associated with cell division in zebrafish embryo.

Recent studies suggested that a Ca(2+) signal is involved in the regulation of cell division. For example, using a confocal imaging technique, we have shown that a localized Ca(2+) elevation was clearly associated with the onset of cytokinesis in zebrafish embryo [Chang and Meng (1995) J. Cell Biol. 131:1539-1545]. This finding was later confirmed in studies using aequorin as a Ca(2+) probe. Here, we used a 4-D confocal measurement technique to further characterize the properties of the Ca(2+) signal associated with cell division. We found evidence that there were three types of Ca(2+) signals associated with different stages of cell cleavage in embryonic cell. The first type was repetitive Ca(2+) spikes that emerged several minutes before the first cell cleavage began. These Ca(2+) spikes were first distributed broadly over the central region of the blastodisc and then gradually localized in the equatorial region; they appeared to play the role of determining the position of the first cleavage plane. The second type was a calcium wave that propagated along the cleavage furrow and appeared to guide the furrow extension during the progression of cytokinesis. The third type was a group of post-cleavage calcium spikes that appeared to be responsible for furrow deepening and maintenance of the contractile band. When this type of Ca(2+) transient was blocked by injecting BAPTA or heparin, cell cleavage regressed and the structure of the contractile band could no longer be maintained.

Animals↗
PubMed1998

Calcium signalling in exocrine glands.

In exocrine gland cells, stimulation of a variety of surface receptors initiates a Ca2+ signalling system through activation of a polyphosphoinositide-specific phospholipase C. One product of phospholipase C activity, inositol 1,4,5-trisphosphate ((1,4,5)IP3), signals the release of intracellular Ca2+. Release of intracellular Ca2+ is followed by entry of Ca2+ into the cell across the plasma membrane. The mechanism by which Ca2+ entry is regulated is not well understood, although it is clear that (1,4,5)IP3 plays an important role. One hypothesis suggests that Ca2+ entry is triggered by the depletion of intracellular Ca2+ stores by (1,4,5)IP3, a process termed 'capacitative calcium entry'. The purpose of these studies is to gain understanding into the processes controlling capacitative calcium entry in exocrine gland cells.

Animals↗
PubMed2004

Wine polyphenols stimulate superoxide anion production to promote calcium signaling and endothelial-dependent vasodilatation.

The present study was aimed to evaluate the mechanisms involved in the vasorelaxant effects of red wine polyphenol compounds (RWPC) in small mesenteric rat arteries. RWPC produce relaxation in small mesenteric arteries. This relaxant effect was abolished by endothelial denudation, NO-synthase blockade with L-NAME and partial depolarization with KCl or L-NAME plus KCl. Incubation with the reactive oxygen species scavenger, superoxide dismutase (SOD) plus catalase, or inhibition of NAD(P)H-dependent oxidoreductases with diphenyleneiodonium also inhibited RWPC induced vascular relaxation. Application of RWPC elicited a transient increase in intracellular calcium concentration ([Ca2+]i) in bovine aortic endothelial cells (BAEC), which was attenuated by a mixture of SOD and catalase. Incubation of BAEC with RWPC increased the SOD inhibitable production of O2-. These results suggest the involvement of O2- in the [Ca2+]i increase evoked by RWPC, leading to the activation of enzymes involved in the release of endothelial relaxant factors and subsequent vasodilatation of resistance arteries.

Animals↗
PubMed2005

Inhibition by 2,4-toluene diisocyanate of the calcium signaling of neuronal nicotinic acetylcholine receptors in human neuroblastoma SH-SY5Y cells.

Toluene diisocyanate (TDI) is widely used as a chemical intermediate in the production of polyurethane products such as foams, coatings, and elastomers. In exposed workers, chronic inhalation of TDI has resulted in significant decreases in lung function. TDI-induced asthma is related to its disturbance of acetylcholine in most affected workers but the actions of TDI on nicotinic acetylcholine receptors (nAChR) are unclear. In order to understand the role of TDI acting on nAChR, we used human neuroblastoma SH-SY5Y cells to investigate the effects of TDI on cytosolic free calcium concentration ([Ca2+]c) changes under the stimulation of nAChR. The results showed that TDI was capable of inhibiting the [Ca2+]c rise induced by nicotinic ligands, epibatidine, DMPP and nicotine. The inhibition was remained, even increased after chronic treatment of TDI. Our study of TDI acting on human nAChR suggests a possibility that the human nerve system plays some role in the toxicity of TDI in the pulmonary system.

Bridged Bicyclo Compounds, Heterocyclic↗
PubMed2000

Calcium signaling in the ER: its role in neuronal plasticity and neurodegenerative disorders.

Endoplasmic reticulum (ER) is a multifaceted organelle that regulates protein synthesis and trafficking, cellular responses to stress, and intracellular Ca2+ levels. In neurons, it is distributed between the cellular compartments that regulate plasticity and survival, which include axons, dendrites, growth cones and synaptic terminals. Intriguing communication networks between ER, mitochondria and plasma membrane are being revealed that provide mechanisms for the precise regulation of temporal and spatial aspects of Ca2+ signaling. Alterations in Ca2+ homeostasis in ER contribute to neuronal apoptosis and excitotoxicity, and are being linked to the pathogenesis of several different neurodegenerative disorders, including Alzheimer's disease and stroke.

Animals↗
PubMed2003

Involvement of prenylated proteins in calcium signaling induced by LTD4 in differentiated U937 cells.

We investigated signal transduction pathways for LTD4 in the human promonocytic cell line U937 known, upon differentiation, to express CysLT1 receptors. We confirmed the presence of high-affinity binding sites for 3H-LTD4, which, in functional studies, displayed the features of CysLT1 receptor. In fact, three potent and selective CysLT1 receptor antagonists were able to completely inhibit LTD4-induced response. In turn, cytosolic Ca2+ ([Ca2+]i) increase (EC50 = 3.4 nM +/- 27% CV) was only partially sensitive to pertussis toxin (PTx) as well as to the prenylation inhibitor fluvastatin and to the specific geranylgeranylation and farnesylation inhibitors BAL 9504 and FPT II. Finally, Clostridium sordellii lethal toxin, inhibitor of the Ras family of GTPases, and FTS, a potent methyltransferase inhibitor, were both able to partially inhibit LTD4-induced [Ca2+] increase, suggesting a role for a Ras family member in [Ca2+]i regulation. In conclusion, in dU937 LTD4 signal transduction involves: (a) at least two pathways, one sensitive and one insensitive to PTx; (b) isoprenylated proteins, such as betagamma subunits and, possibly, a small G protein of the Ras family.

Bacterial Toxins↗