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At least 937 records · Page 52Linked to original sources
PubMed2001

Microtubule disruption by colchicine reversibly enhances calcium signaling in intact rat cardiac myocytes.

Using the whole-cell patch-clamp configuration in rat ventricular myocytes, we recently reported that microtubule disruption increases calcium current (I(Ca)) and [Ca(2+)](i) transient and accelerates their kinetics by adenylyl cyclase activation. In the present report, we further analyzed the effects of microtubule disruption by 1 micromol/L colchicine on Ca(2+) signaling in cardiac myocytes with intact sarcolemma. In quiescent intact cells, it is possible to investigate ryanodine receptor (RyR) activity by analyzing the characteristics of spontaneous Ca(2+) sparks. Colchicine treatment decreased Ca(2+) spark amplitude (F/F(0): 1.78+/-0.01, n=983, versus 1.64+/-0.01, n=1660, recorded in control versus colchicine-treated cells; P<0.0001) without modifying the sarcoplasmic reticulum Ca(2+) load and enhanced their time to peak (in ms: 6.85+/-0.09, n=1185, versus 7.33+/-0.13, n=1647; P<0.0001). Microtubule disruption also induced the appearance of Ca(2+) sparks in doublets. These alterations may reflect RyR phosphorylation. To further investigate Ca(2+) signaling in cardiac myocytes with intact sarcolemma, we analyzed [Ca(2+)](i) transient evoked by field stimulation. Cells were loaded with the fluorescence Ca(2+) indicator, Fluo-3 cell permeant, and stimulated at 1 HZ: [Ca(2+)](i) transient amplitude was greater and its decay was accelerated in colchicine-treated, field-stimulated myocytes. This effect is reversible. When colchicine-treated myocytes were placed in a colchicine-free solution for 30 minutes, tubulin was repolymerized into microtubules, as shown by immunofluorescence, and the increase in [Ca(2+)](i) transient was reversed. In summary, we demonstrate that microtubule disruption by colchicine reversibly modulates Ca(2+) signaling in cardiac cells with intact sarcolemma.

Animals↗
PubMed2004

Fertilisation calcium signals in the ascidian egg.

The egg of ascidians (urochordate), as virtually all animal and plant species, displays Ca2+ signals upon fertilisation. These Ca2+ signals are repetitive Ca2+ waves that initiate in the cortex of the egg and spread through the whole egg interior. Two series of Ca2+ waves triggered from two distinct Ca2+ wave pacemakers entrain the two meiotic divisions preceding entry into the first interphase. The second messenger inositol (1,4,5) trisphosphate (IP3) is the main mediator of these global Ca2+ waves. Other Ca2+ signalling pathways (RyR and NAADPR) are functional in the egg but they mediate localised cortical Ca2+ signals whose physiological significance remains unclear. The meiosis I Ca2+ wave pacemaker is mobile and relies on intracellular Ca2+ release from the endoplasmic reticulum (ER) induced by a large production of IP3 at the sperm aster site. The meiosis II Ca2+ wave pacemaker is stably localised in a vegetal protrusion called the contraction pole. It is probable that a local production of IP3 in the contraction pole determines the site of this second pacemaker while functional interactions between ER and mitochondria regulate its activity. Finally, a third ectopic pacemaker can be induced by a global increase in IP3, making the ascidian egg a unique system where three different Ca2+ wave pacemakers coexist in the same cell.

Animals↗
PubMed2006

Control of cell migration in the zebrafish lateral line: implication of the gene "tumour-associated calcium signal transducer," tacstd.

The sensory organs of the zebrafish lateral-line system (neuromasts) originate from migrating primordia that move along precise pathways. The posterior primordium, which deposits the neuromasts on the body and tail of the embryo, migrates along the horizontal myoseptum from the otic region to the tip of the tail. This migration is controlled by the chemokine SDF1, which is expressed along the prospective pathway, and by its receptor CXCR4, which is expressed by the migrating cells. In this report, we describe another zebrafish gene that is heterogeneously expressed in the migrating cells, tacstd. This gene codes for a membrane protein that is homologous to the TACSTD1/2 mammalian proteins. Inactivation of the zebrafish tacstd gene results in a decrease in proneuromast deposition, suggesting that tacstd is required for the deposition process.

Amino Acid Sequence↗
PubMed2006

Calcium signaling in Schwann cells at synaptic and extra-synaptic sites: active glial modulation of neuronal activity.

Glial cells are widely dispersed in the central nervous system (CNS) as well as in the peripheral nervous system (PNS). In the PNS, perisynaptic Schwann cells (PSCs) are the glial cells associated with the pre- and postsynaptic elements of the neuromuscular junction (NMJ). They, as other glial cells of the CNS, respond to high-frequency motor nerve stimulation with an increase in intracellular Ca(2+). In addition to detecting and responding to neurotransmission, PSCs are involved in short-term plasticity events where they depress neurotransmission through G-protein-dependent mechanisms and potentiate synaptic activity via Ca(2+)-dependent mechanisms. In this review, we will discuss evidence that outlines the role of PSCs in short- and long-term modulation of synaptic activity. We will also emphasize present functional similarities and differences in PSC activation at different NMJs. The importance of glial-neural interactions along myelinating axons will also be discussed.

Animals↗
PubMed2000

The effects of inhibiting myosin light chain kinase on contraction and calcium signalling in human and rat myometrium.

The effect of inhibiting myosin light chain kinase on contractions of human and rat myometrium has been investigated, to determine whether force can be produced independently of myosin phosphorylation. Two inhibitors were used, wortmannin and ML-9, and their effects on spontaneous, high-K-depolarization-induced and oxytocin-induced force studied. Both inhibitors reduced and then abolished uterine force, irrespective of how it was produced; this was the case for both human and rat myometrium, and pregnant and non-pregnant tissue. The effects of wortmannin on intracellular [Ca2+] and inward Ca2+ current were examined. The data showed that the reduction in force produced by wortmannin occurs without a reduction of either the Ca2+ current or [Ca2+]. It is concluded that, under normal physiological conditions, myosin light chain kinase phosphorylation of myosin is essential for uterine force production and that there is little or no role for alternative force-producing pathways.

Adolescent↗
PubMedDate not supplied

Glial calcium signaling and neuron-glia communication.

The existence of bidirectional signaling between astrocytes and neurons has revealed an important active role of astrocytes in the physiology of the nervous system. As a consequence, there is a new concept of the synaptic physiology-"the tripartite synapse", where astrocytes exchange information with the pre- and postsynaptic elements and participate as dynamic regulatory elements in neurotransmission. The control of the Ca2+ excitability in astrocytes is a key element in this loop of information exchange. The ability of astrocytes to respond to neuronal activity and discriminate between the activity of different synapses, the modulation of the astrocytic cellular excitability by the synaptic activity, and the expression of cellular intrinsic properties indicate that astrocytes are endowed with cellular computational characteristics that process synaptic information. Therefore, we propose that astrocytes can be considered as cellular elements involved in the information processing by the nervous system.

Animals↗
PubMed2006

Nuclear calcium signals during L-LTP induction do not predict the degree of synaptic potentiation.

The magnitude and/or duration of nuclear Ca(2+)-transients has been shown to dose-dependently modulate gene transcription upon neuronal activation. This is an attractive model for synapse-to-nucleus communication. In order to encode synaptic information, these nuclear Ca(2+)-transients have to be correlated with changes in synaptic strength rather than changes in gene expression patterns. In this study, we analysed nuclear Ca(2+) signals during L-LTP induction. Using a combined approach of fEPSP recordings and two-photon imaging, these Ca(2+) signals were correlated with different degrees of synaptic potentiation in CA1 hippocampal slices. To refine our analysis on the single-cell level, we developed a new approach called single-cell-excitability-probing (SCEP) to assay the plasticity outcome of individual cells by optical means. The degrees of synaptic potentiation we observed could be categorized into transcription independent, transcription-dependent and reduced transcription-dependent. There is no consistent dose-dependent relationship between these different degrees of synaptic potentiation and the magnitude, the decay time and the area under the curve of nuclear Ca(2+)-transients during L-LTP induction. This indicates that nuclear Ca(2+)-transients during induction are unsuited to grade the degree of plasticity in an analogue manner. We propose a role for nuclear Ca(2+) as a digital on/off switch for activating transcription.

Animals↗
PubMed2004

Abnormal calcium signaling and sudden cardiac death associated with mutation of calsequestrin.

Mutations in human cardiac calsequestrin (CASQ2), a high-capacity calcium-binding protein located in the sarcoplasmic reticulum (SR), have recently been linked to effort-induced ventricular arrhythmia and sudden death (catecholaminergic polymorphic ventricular tachycardia). However, the precise mechanisms through which these mutations affect SR function and lead to arrhythmia are presently unknown. In this study, we explored the effect of adenoviral-directed expression of a canine CASQ2 protein carrying the catecholaminergic polymorphic ventricular tachycardia-linked mutation D307H (CASQ2(D307H)) on Ca2+ signaling in adult rat myocytes. Total CASQ2 protein levels were consistently elevated approximately 4-fold in cells infected with adenoviruses expressing either wild-type CASQ2 (CASQ2(WT)) or CASQ2(D307H). Expression of CASQ2(D307H) reduced the Ca2+ storing capacity of the SR. In addition, the amplitude, duration, and rise time of macroscopic I(Ca)-induced Ca2+ transients and of spontaneous Ca2+ sparks were reduced significantly in myocytes expressing CASQ2(D307H). Myocytes expressing CASQ2(D307H) also displayed drastic disturbances of rhythmic oscillations in [Ca2+]i and membrane potential, with signs of delayed afterdepolarizations when undergoing periodic pacing and exposed to isoproterenol. Importantly, normal rhythmic activity was restored by loading the SR with the low-affinity Ca2+ buffer, citrate. Our data suggest that the arrhythmogenic CASQ2(D307H) mutation impairs SR Ca2+ storing and release functions and destabilizes the Ca2+-induced Ca2+ release mechanism by reducing the effective Ca2+ buffering inside the SR and/or by altering the responsiveness of the Ca2+ release channel complex to luminal Ca2+. These results establish at the cellular level the pathological link between CASQ2 mutations and the predisposition to adrenergically mediated arrhythmias observed in patients carrying CASQ2 defects.

Adenoviridae↗
PubMed2000

Interactions between hypoxia and hypercapnic acidosis on calcium signaling in carotid body type I cells.

The effects of hypercapnic acidosis and hypoxia on intracellular Ca(2+) concentration ([Ca(2+)](i)) were determined with Indo 1 in enzymatically isolated single type I cells from neonatal rat carotid bodies. Type I cells responded to graded hypoxic stimuli with graded [Ca(2+)](i) rises. The percentage of cells responding was also dependent on the severity of the hypoxic stimulus. Raising CO(2) from 5 to 10 or 20% elicited a significant increase in [Ca(2+)](i) in the same cells as those that responded to hypoxia. Thus both stimuli can be sensed by each individual cell. When combinations of hypoxic and acidic stimuli were given simultaneously, the responses were invariably greater than the response to either stimulus given alone. Indeed, in most cases, the response to hypercapnia was slightly potentiated by hypoxia. These data provide the first evidence that the classic synergy between hypoxic and hypercapnic stimuli observed in the intact carotid body may, in part, be an inherent property of the type I cell.

Acidosis↗
PubMed2005

The prion protein and its paralogue Doppel affect calcium signaling in Chinese hamster ovary cells.

The function of the prion protein (PrP(c)), implicated in transmissible spongiform encephalopathies (TSEs), is largely unknown. We examined the possible influence of PrP(c) on Ca(2+) homeostasis, by analyzing local Ca(2+) fluctuations in cells transfected with PrP(c) and Ca(2+)-sensitive aequorin chimeras targeted to defined subcellular compartments. In agonist-stimulated cells, the presence of PrP(c) sharply increases the Ca(2+) concentration of subplasma membrane Ca(2+) domains, a feature that may explain the impairment of Ca(2+)-dependent neuronal excitability observed in TSEs. PrP(c) also limits Ca(2+) release from the endoplasmic reticulum and Ca(2+) uptake by mitochondria, thus rendering unlikely the triggering of cell death pathways. Instead, cells expressing Doppel, a PrP(c) paralogue, display opposite effects, which, however, are abolished by the coexpression of PrP(c). These findings are consistent with the functional interplay and antagonistic role attributed to the proteins, whereby PrP(c) protects, and Doppel sensitizes, cells toward stress conditions.

Adenosine Triphosphate↗
PubMed2001

[Effect of arachidonic and other fatty acids on the intracellular calcium concentration and calcium signaling in peritoneal macrophages].

Effects of arachidonic and other fatty acids on the intracellular Ca2+ concentration ([Ca2+]i) in rat peritoneal macrophages was investigated. It has been shown that cis-polyunsaturated arachidonic and linoleic induce a significant and dose-dependent increase in [Ca2+]i, which is due to depletion of thapsigargin-sensitive Ca2+ store and to stimulation of Ca2+ entry from the extracellular medium. Pharmacological characteristics of Ca2+ entry induced by arachidonic acid appeared to be similar to those of store-dependent Ca2+ entry activated by thapsigargin or cyclopiazonic acid; Ca2+ entry is attenuated by the same Ca2+ channel inhibitors, by tyrosine kinase inhibitor genistein and epoxygenase inhibitor proadifen. Cis-monounsaturated oleic and saturated myristic acids appeared to be less effective and induced only a slight increase in [Ca2+]i at much higher concentrations. Arachidonic and other fatty acids can also stimulate Ca(2+)-ATPase in the macrophage plasma membrane. The data are compatible with the important role played by arachidonic and other free fatty acids in the regulation of [Ca2+]i in peritoneal macrophages.

Animals↗
PubMed1998

Angiotensin AT1B receptor mediates calcium signaling in vascular smooth muscle cells of AT1A receptor-deficient mice.

Our studies on angiotensin II receptor subtype 1A (AT1A) knockout mice define how endogenous receptors other than AT1A receptors stimulate changes in cytosolic calcium concentration ([Ca2+]i) in cultured aortic vascular smooth muscle cells (VSMCs). Wild-type cells have a 1.7 ratio of AT1A/AT1B receptor mRNA as determined by semiquantitative reverse transcriptase-polymerase chain reaction. Mutant cells express AT1B receptor mRNA but not that for the AT1A receptor. In wild-type cells with AT1A present, Ang II (10(-7) mol/L) produces a characteristic rapid peak increase in [Ca2+]i of 150 to 180 nmol/L, followed by a plateau phase characterized by a sustained 70 to 80 nmol/L increase in [Ca2+]i. An unexpected finding was that the magnitude and time-dependent pattern of [Ca2+]i changes produced by Ang II were similar in cells that lacked AT1A receptors but possessed AT1B receptors. The response in mutant cells indicates effective coupling of an Ang II receptor to one or more second messenger systems. The similarity of response patterns between cells with and without AT1A receptors suggests that non-AT1A receptors are functionally linked to similar signal transduction pathways in mutant cells. The fact that mutant and wild-type cells exhibit similar patterns of calcium mobilization and entry supports the notion that AT1A and non-AT1A receptors share common signal transduction pathways. The AT2 receptor ligands PD-123319 and CGP-42112 do not alter Ang II effects in either VSMC type, suggesting a paucity of AT2 receptors and/or an absence of their linkage to [Ca2+]i pathways. The nonpeptide AT1 receptor blocker losartan antagonizes Ang II-induced [Ca2+]i increases in both cell groups, supporting mediation by native AT1B receptors and effective coupling of this subtype to second messenger systems leading to calcium entry and mobilization. Our results demonstrate that Ang II causes calcium signaling in AT1A-deficient VSMCs that is mediated by an endogenous losartan-sensitive AT1B receptor.

Angiotensin II↗
PubMed2006

Functional role of calcium signals for microglial function.

In this review we summarize mechanisms of Ca(2+) signaling in microglial cells and the impact of Ca(2+) signaling and Ca(2+) levels on microglial function. So far, Ca(2+) signaling has been only characterized in cultured microglia and thus these data refer rather to activated microglia as observed in pathology when compared with the resting form found under physiological conditions. Purinergic receptors are the most prominently expressed ligand-gated Ca(2+)-permeable channels in microglia and control several microglial functions such as cytokine release in a Ca(2+)-dependent fashion. A large variety of metabotropic receptors are linked to Ca(2+) release from intracellular stores. Depletion of these intracellular stores triggers a capacitative Ca(2+) entry. While microglia are already in an activated state in culture, they can be further activated, for example, by exposure to bacterial endotoxin. This activation leads to a chronic increase of [Ca(2+)](i) and this Ca(2+) increase is a prerequisite for the release of nitric oxide and cytokines. Moreover, several factors (TNFalpha, IL-1beta, and IFN-gamma) regulate resting [Ca(2+)](i) levels.

Animals↗
PubMed2000

Intracellular calcium signalling in magnocellular neurones of the rat supraoptic nucleus: understanding the autoregulatory mechanisms.

Oxytocin and vasopressin, released at the soma and dendrites of neurones, bind to specific autoreceptors and induce an increase in [Ca2+]i. In oxytocin cells, the increase results from a mobilisation of Ca2+ from intracellular stores, whereas in vasopressin cells, it results mainly from an influx of Ca2+ through voltage-dependent channels. The response to vasopressin is coupled to phospholipase C and adenylyl-cyclase pathways which are activated by V1 (V1a and V1b)- and V2-type receptors respectively. Measurements of [Ca2+]i in response to V1a and V2 agonists and antagonists suggest the functional expression of these two types of receptors in vasopressin neurones. The intracellular mechanisms involved are similar to those observed for the action of the pituitary adenylyl-cyclase-activating peptide (PACAP). Isolated vasopressin neurones exhibit spontaneous [Ca2+]i oscillations and these are synchronised with phasic bursts of electrical activity. Vasopressin modulates these spontaneous [Ca2+]i oscillations in a manner that depends on the initial state of the neurone, and such varied effects of vasopressin may be related to those observed on the electrical activity of vasopressin neurones in vivo.

Animals↗
PubMed2002

Spatial segregation and interaction of calcium signalling mechanisms in rat hippocampal CA1 pyramidal neurons.

Postsynaptic [Ca2+]i increases result from Ca2+ entry through ligand-gated channels, entry through voltage-gated channels, or release from intracellular stores. We found that these sources have distinct spatial distributions in hippocampal CA1 pyramidal neurons. Large amplitude regenerative release of Ca2+ from IP3-sensitive stores in the form of Ca2+ waves were found almost exclusively on the thick apical shaft. Smaller release events did not extend more than 15 microm into the oblique dendrites. These synaptically activated regenerative waves initiated at points where the stimulated oblique dendrites branch from the apical shaft. In contrast, NMDA receptor-mediated increases were observed predominantly in oblique dendrites where spines are found at high density. These [Ca2+]i increases were typically more than eight times larger than [Ca2+]i from this source on the main aspiny apical shaft. Ca2+ entry through voltage-gated channels, activated by backpropagating action potentials, was detected at all dendritic locations. These mechanisms were not independent. Ca2+ entry through NMDA receptor channels or voltage-gated channels (as previously demonstrated) synergistically enhanced Ca2+ release generated by mGluR mobilization of IP3.

Action Potentials↗
PubMed2003

Calcium signaling mediated by P2Y receptors in mouse taste cells.

Evidence implicates a number of neuroactive substances and their receptors in mediating complex cell-to-cell communications in the taste bud. Recently, we found that ATP, a ubiquitous neurotransmitter/neuromodulator, mobilizes intracellular Ca2+ in taste cells by activating P2Y receptors. Here, P2Y receptor-cellular response coupling was characterized in detail using single cell ratio photometry and the inhibitory analysis. The sequence of underlying events was shown to include ATP-dependent activation of PLC, IP3 production, and IP3 receptor-mediated Ca2+ release followed by Ca2+ influx. Data obtained favor SOC channels rather than receptor-operated channels as a pathway for Ca2+ influx that accompanies Ca2+ release. Intracellular Ca2+ mobilized by ATP is apparently extruded by the plasma membrane Ca2+-ATPase, while a contribution of the Na+/Ca2+ exchange and other mechanisms of Ca2+ clearance is negligible. Cyclic AMP-dependent phosphorylation is likely to control a gain of the phosphoinositide cascade involved in ATP transduction. ATP-responsive taste cells are abundant in circumvallate, foliate, and fungiform papillae. Taken together, our observations point to a putative role for ATP as a neurotransmitter operative in the taste bud.

Adenosine Triphosphate↗
PubMed1999

Amplification of calcium signals at dendritic spines provides a method for CNS quantal analysis.

It has been proposed that the small volume of a dendritic spine can amplify Ca2+ signals during synaptic transmission. Accordingly, we have performed calculations to determine whether the activation of N-methyl-D-aspartate (NMDA) type glutamate receptors during synaptic transmission results in significant elevation in intracellular Ca2+ levels, permitting optical detection of synaptic signals within a single spine. Simple calculations suggest that the opening of even a single NMDA receptor would result in the influx of approximately 310 000 Ca2+ ions into the small volume of a spine, producing changes in Ca2+ levels that are readily detectable using high affinity Ca2+ indicators such as fura-2 or fluo-3. Using fluorescent Ca2+ indicators, we have imaged local Ca2+ transients mediated by NMDA receptors in spines and dendritic shafts attributed to spontaneous miniature synaptic activity. Detailed analysis of these quantal events suggests that the current triggering these transients is attributed to the activation of <10 NMDA receptors. The frequency of these miniature synaptic Ca2+ transients is not randomly distributed across synapses, as some synapses can display a >10-fold higher frequency of transients than others. As expected for events mediated by NMDA receptors, miniature synaptic Ca2+ transients were suppressed by extracellular Mg2+ at negative membrane potentials; however, the Mg2+ block could be removed by depolarization.

Animals↗
PubMed2004

Norepinephrine-induced calcium signaling and expression of adrenoceptors in avian tendon cells.

Sympathetic efferent nerves are present in tendons, but their function within tendon is unknown. alpha(1)-Adrenoceptors are expressed by a variety of cell types. In the presence of norepinephrine (NE), adrenoceptors activate G(q/11) signaling pathways that subsequently increase intracellular Ca(2+) concentration ([Ca(2+)](ic)). It was hypothesized that avian tendon cells express functional adrenoceptors that respond to NE by increasing [Ca(2+)](ic). Avian tendon cells were analyzed for mRNA expression of alpha(1)-adrenoceptors by RT-PCR. Avian tendons expressed the alpha(1A)- and alpha(1B)-adrenoceptor subtypes. Furthermore, both tendon surface epitenon cells and internal fibroblasts infused with a Ca(2+)-sensitive dye, fura 2, and stimulated with NE responded by increasing [Ca(2+)](ic). KMD-3213, an alpha(1A)-adrenoceptor antagonist, significantly reduced the Ca(2+) response. Other adrenoceptor antagonists had no effect on the Ca(2+) response. The absence of extracellular Ca(2+) also significantly reduced the response to NE, indicating that Ca(2+) influx contributed to the rise in [Ca(2+)](ic). This study provides the first evidence that tendon cells express adrenoceptors and that the NE-induced Ca(2+) response is coupled to the alpha(1A)-adrenoceptor subtype.

Adrenergic Antagonists↗