Modulation of Ca2+ Signaling by Na+/Ca2+ Exchangers in Mast Cells

Aneiros, Eduardo; Philipp, Stephan E.; Lis, Annette; Freichel, Marc; Cavalié, Adolfo

doi:10.4049/jimmunol.174.1.119

Cited by 54 publications

(36 citation statements)

References 36 publications

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“…A similar cross-talk has been proposed to exist between CRAC channels and the plasma membrane Na ϩ /Ca 2ϩ exchanger (NCX) in mast cells (34). Nevertheless, the relative contribution of these systems to the control of local [Ca 2ϩ ] varies significantly with the experimental conditions used, the time window analyzed and the cell type under study.…”

Section: Discussionmentioning

confidence: 77%

ATP from Subplasmalemmal Mitochondria Controls Ca2+-dependent Inactivation of CRAC Channels

Montalvo¹,

Artalejo

Gilabert

2006

Journal of Biological Chemistry

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A sustained Ca2؉ entry is the primary signal for T lymphocyte activation after antigen recognition. This Ca 2؉ entry mainly occurs through store-operated Ca 2؉ channels responsible for a highly selective Ca 2؉ current known as I CRAC . Ca 2؉ ions act as negative feedback regulators of I CRAC , promoting its inactivation. Mitochondria, which act as intracellular Ca 2؉ buffers, have been proposed to control all stages of CRAC current and, hence, intracellular Ca 2؉ signaling in several types of non-excitable cells. Using the whole-cell configuration of the patch clamp technique, which allows control of the intracellular environment, we report here that respiring mitochondria located close to CRAC channels can regulate slow Ca 2؉ -dependent inactivation of I CRAC by increasing the Ca 2؉ -buffering capacity beneath the plasma membrane, mainly through the release of ATP.

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Section: Discussionmentioning

confidence: 77%

ATP from Subplasmalemmal Mitochondria Controls Ca2+-dependent Inactivation of CRAC Channels

Montalvo¹,

Artalejo

Gilabert

2006

Journal of Biological Chemistry

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“…This, therefore, explains the role of the exchanger not only in E-C coupling, but also in the control of the neurosecretion processes (42,43,133). Furthermore, the Na 2ϩ /Ca 2ϩ exchanger, working in the extrusion mode, has being recently implicated in the modulation of Ca 2ϩ signal in mast cells (7). Finally, there are numerous reports that link the Na ϩ /Ca 2ϩ exchanger with many pathophysiological syndromes including heart arrhythmias, all salt-dependent hypertension, reperfusion injury, and cardiac ischemia, among others (34,35,40,43,173,185,193,238,241,255).…”

Section: Discovery Evolution Of the Field In Time And Physiologimentioning

confidence: 99%

Sodium/Calcium Exchanger: Influence of Metabolic Regulation on Ion Carrier Interactions

DiPolo¹,

Beaugé²

2006

Physiological Reviews

192

157

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The Na+/Ca2+ exchanger's family of membrane transporters is widely distributed in cells and tissues of the animal kingdom and constitutes one of the most important mechanisms for extruding Ca2+ from the cell. Two basic properties characterize them. 1) Their activity is not predicted by thermodynamic parameters of classical electrogenic countertransporters (dependence on ionic gradients and membrane potential), but is markedly regulated by transported (Na+ and Ca2+) and nontransported ionic species (protons and other monovalent cations). These modulations take place at specific sites in the exchanger protein located at extra-, intra-, and transmembrane protein domains. 2) Exchange activity is also regulated by the metabolic state of the cell. The mammalian and invertebrate preparations share MgATP in that role; the squid has an additional compound, phosphoarginine. This review emphasizes the interrelationships between ionic and metabolic modulations of Na+/Ca2+ exchange, focusing mainly in two preparations where most of the studies have been carried out: the mammalian heart and the squid giant axon. A surprising fact that emerges when comparing the MgATP-related pathways in these two systems is that although they are different (phosphatidylinositol bisphosphate in the cardiac and a soluble cytosolic regulatory protein in the squid), their final target effects are essentially similar: Na+-Ca2+-H+ interactions with the exchanger. A model integrating both ionic and metabolic interactions in the regulation of the exchanger is discussed in detail as well as its relevance in cellular Cai2+ homeostasis.

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“…Interestingly, preliminary studies in murine macrophages [14] and human basophils [15] have suggested the presence of NCX in immune cells. NCX activities have also been reported in human lymphocytes [16], neutrophils [17], and rat mast cells [18,19] investigated using pharmacological agents. In these cells, NCX may contribute either to the extrusion of Ca 21 after Ca 21 -spiking events or to the increase in [Ca 21 ] i during cell activation.…”

Section: Introductionmentioning

confidence: 99%

Expression and function of Na⁺/Ca²⁺ exchangers 1 and 3 in human macrophages and monocytes

et al. 2009

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The Na 1 /Ca 21 exchanger (NCX) is a membrane transporter that can switch Na 1 and Ca 21 in either direction to maintain the homeostasis of intracellular Ca 21 . Three isoforms (NCX1, NCX2, and NCX3) have been characterized in excitable cells, e.g. neurons and muscle cells. We examined the expression of these NCX isoforms in primary human lung macrophages (HLM) and blood monocytes. NCX1 and NCX3, but not NCX2, are expressed in HLM and monocytes at both mRNA and protein levels. Na 1 -free medium induced a significant increase in intracellular calcium concentration ([Ca 21 ] i ) in both cell types. This response was completely abolished by the NCX inhibitor 5-(N-4-chlorobenzyl)-20,40-dimethylbenzamil (CB-DMB). Moreover, inhibition of NCX activity during Ca 21 -signaling induced by histamine caused a delay in restoring baseline [Ca 21 ] i . Na 1 -free medium induced TNF-a expression and release in HLM comparable to that caused by LPS. TNF-a release induced by Na 1 -free medium was blocked by CB-DMB and greatly reduced by RNAi-mediated knockdown of NCX1. These results indicate that human macrophages and monocytes express NCX1 and NCX3 that operate in a bidirectional manner to restore [Ca 21 ] i , to generate Ca 21 -signals, and to induce TNF-a production. Therefore, NCX may contribute to regulate Ca 21 homeostasis and proinflammatory functions in human macrophages and monocytes.Key words: Ca 21 -signaling . Macrophages . Monocytes . Na 1 /Ca 21 exchanger IntroductionThe Na 1 /Ca 21 exchanger (NCX) is a plasma membrane protein involved in the homeostasis of intracellular Ca 21 [1]. NCX is a bidirectional ion transporter that catalyzes the exchange of Na 1 and Ca 21 depending on their electrochemical gradients [2]. Under physiological conditions, NCX's primary role is to extrude Ca 21 from cells using the Na 1 gradient across the cell membrane (forward mode of operation) [3]. However, in some cases it can contribute to the Ca 21 influx into the cells by working in the reverse mode (i.e. coupling Ca 21 influx with Na 1 efflux) [4][5][6].Three isoforms of NCX, NCX1, NCX2, and NCX3 have been cloned in mammals, outlining a multigene family whose members share a similar molecular structure [7]. NCX is modeled with nine transmembrane segments involved in ion transport and a long central cytoplasmic loop that has regulatory functions [8]. However, truncated forms lacking certain transmembrane segments, but still possessing NCX activity, have also been Eur. J. Immunol. 2009. 39: 1405-1418 DOI 10.1002 Leukocyte signaling 1405 described as the result of alternative splicing of the three genes [9][10][11]. NCX1 is largely predominant in mammalian tissues such as heart, brain, and kidney while the expression of NCX2 and NCX3 appears to be limited to the brain and skeletal muscle [7]. NCX is a key element regulating intracellular Ca 21 concentrations ([Ca 21 ] i ) in many excitable cells, including myocardiocytes, retinal rod photoreceptors, smooth muscle cells, and neurons [3]. Non-excitable cells such as renal epithelial ce...

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Modulation of Ca2+ Signaling by Na+/Ca2+ Exchangers in Mast Cells

Cited by 54 publications

References 36 publications

ATP from Subplasmalemmal Mitochondria Controls Ca2+-dependent Inactivation of CRAC Channels

ATP from Subplasmalemmal Mitochondria Controls Ca2+-dependent Inactivation of CRAC Channels

Sodium/Calcium Exchanger: Influence of Metabolic Regulation on Ion Carrier Interactions

Expression and function of Na⁺/Ca²⁺ exchangers 1 and 3 in human macrophages and monocytes

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Modulation of Ca2+ Signaling by Na+/Ca2+ Exchangers in Mast Cells

Cited by 54 publications

References 36 publications

ATP from Subplasmalemmal Mitochondria Controls Ca2+-dependent Inactivation of CRAC Channels

ATP from Subplasmalemmal Mitochondria Controls Ca2+-dependent Inactivation of CRAC Channels

Sodium/Calcium Exchanger: Influence of Metabolic Regulation on Ion Carrier Interactions

Expression and function of Na+/Ca2+ exchangers 1 and 3 in human macrophages and monocytes

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Expression and function of Na⁺/Ca²⁺ exchangers 1 and 3 in human macrophages and monocytes