Na+-Ca2+ Exchanger Expression and Its Modulation

Kimura, Junko; Ono, Tomoyuki; Sakamoto, Kazuho; Ito, Emi; Watanabe, Shinya; Maeda, Sachiko; Shikama, Yayoi; Yatabe, Midori; Matsuoka, Isao

doi:10.1248/bpb.32.325

Cited by 11 publications

(11 citation statements)

References 43 publications

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“…NCX1 was ubiquitously characterized and cloned (in organs such as the heart, brain, and kidney and at lower levels in other tissues), while NCX2 and NCX3 were selectively expressed in the brain, skeletal muscle, and selected neuronal populations [1,3,4,10]. In the current study, NCX1, NCX2, and NCX3 expression pattern in the TG neurons was similar to that in the cerebrum [3], but not to that in myocardium. Expression of all NCX isoforms has been reported to be much higher in neurons than in astrocytes [20,21].…”

Section: Discussionmentioning

confidence: 99%

Sodium-Calcium Exchangers in Rat Trigeminal Ganglion Neurons

et al. 2013

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BackgroundNoxious stimulation and nerve injury induce an increase in intracellular Ca2+ concentration ([Ca2+]i) via various receptors or ionic channels. While an increase in [Ca2+]i excites neurons, [Ca2+]i overload elicits cytotoxicity, resulting in cell death. Intracellular Ca2+ is essential for many signal transduction mechanisms, and its level is precisely regulated by the Ca2+ extrusion system in the plasma membrane, which includes the Na+-Ca2+ exchanger (NCX). It has been demonstrated that Ca2+-ATPase is the primary mechanism for removing [Ca2+]i following excitatory activity in trigeminal ganglion (TG) neurons; however, the role of NCXs in this process has yet to be clarified. The goal of this study was to examine the expression/localization of NCXs in TG neurons and to evaluate their functional properties.ResultsNCX isoforms (NCX1, NCX2, and NCX3) were expressed in primary cultured rat TG neurons. All the NCX isoforms were also expressed in A-, peptidergic C-, and non-peptidergic C-neurons, and located not only in the somata, dendrites, axons and perinuclear region, but also in axons innervating the dental pulp. Reverse NCX activity was clearly observed in TG neurons. The inactivation kinetics of voltage-dependent Na+ channels were prolonged by NCX inhibitors when [Ca2+]i in TG neurons was elevated beyond physiological levels.ConclusionsOur results suggest that NCXs in TG neurons play an important role in regulating Ca2+-homeostasis and somatosensory information processing by functionally coupling with voltage-dependent Na+ channels.

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Section: Discussionmentioning

confidence: 99%

Sodium-Calcium Exchangers in Rat Trigeminal Ganglion Neurons

et al. 2013

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“…Cardiac myocytes express sarcolemmal NCX protein at high levels, and when it is upregulated/overexpressed, it mediates Ca + 2 influx (instead of efflux) during the cardiac action potential (140). Cardiac NCX (encoded by the gene NCX1) consists of nine transmembrane domains, and intramolecular disulfide bonds between cysteine residues of different domains have been implicated to be functionally relevant (136). The activity of the cardiac NCX is sensitive to modification by ROS.…”

Section: B Plasmalemmal Camentioning

confidence: 99%

Redox Control of Cardiac Excitability

Aggarwal

Makielski

2013

Antioxidants & Redox Signaling

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Reactive oxygen species (ROS) have been associated with various human diseases, and considerable attention has been paid to investigate their physiological effects. Various ROS are synthesized in the mitochondria and accumulate in the cytoplasm if the cellular antioxidant defense mechanism fails. The critical balance of this ROS synthesis and antioxidant defense systems is termed the redox system of the cell. Various cardiovascular diseases have also been affected by redox to different degrees. ROS have been indicated as both detrimental and protective, via different cellular pathways, for cardiac myocyte functions, electrophysiology, and pharmacology. Mostly, the ROS functions depend on the type and amount of ROS synthesized. While the literature clearly indicates ROS effects on cardiac contractility, their effects on cardiac excitability are relatively under appreciated. Cardiac excitability depends on the functions of various cardiac sarcolemal or mitochondrial ion channels carrying various depolarizing or repolarizing currents that also maintain cellular ionic homeostasis. ROS alter the functions of these ion channels to various degrees to determine excitability by affecting the cellular resting potential and the morphology of the cardiac action potential. Thus, redox balance regulates cardiac excitability, and under pathological regulation, may alter action potential propagation to cause arrhythmia. Understanding how redox affects cellular excitability may lead to potential prophylaxis or treatment for various arrhythmias. This review will focus on the studies of redox and cardiac excitation. Antioxid. Redox Signal. 18, 432-468.

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“…Given the ubiquitous involvement of Ca 2+ dysregulation in AD, it logically presents a variety of potential therapeutic targets for AD prevention and treatments. Na + / Ca 2+ exchangers serve to terminate the increases of the cytosolic Ca 2+ concentration [11]. At least in theory, increased NCX activity contributes to preventing intracellular Ca 2+ from being overload, thereby alleviating neurotoxicity.…”

Section: Discussionmentioning

confidence: 99%

“…Intracellular Ca 2+ concentration is regulated by a variety of systems and mechanisms such as Ca 2+ release from intracellular stores with subsequent stimulation of store operated calcium entry(SOCE) [5,6] and Na + /Ca 2+ exchangers(NCX) [7][8][9][10]. NCX is a transporter that can move sodium across the membrane in exchange for calcium [11][12][13]. The carrier extrudes Ca 2+ at high intracellular Ca 2+ concentration and at hyper-polarized cell membrane potential, whereas at high intracellular Na + concentration and depolarized cell membrane the carrier is reversed thus mediating Ca 2+ entry [14,15].…”

Section: Dysregulation Of Intracellular Camentioning

confidence: 99%

Effects of Leptin on Na+/Ca2+ Exchanger in PC12 Cells

Zhang

Sun

et al. 2016

Cell Physiol Biochem

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Background/Aims: Alzheimer's disease (AD) is known to be related to alterations in neuronal intracellular calcium activity ([Ca²⁺]_i). The present study revealed the distinct role of leptin in Na⁺/Ca²⁺-exchanger activity. Methods: [Ca²⁺]_i was determined utilizing Fura-2 fluorescence. The activity of NCX was measured by removal of extracellular Na⁺ in the presence of external Ca²⁺. Na⁺/Ca²⁺-exchanger activity was further quantified from whole cell currents following removal of extracellular Na⁺. Na⁺/Ca²⁺-exchanger isoform NCX1 transcript levels and protein abundance were quantified by RT-PCR and Western blotting, respectively. Results: Exposure of PC12 cells to 30 µM amyloid (Aβ₄₂) increased [Ca²⁺]_i, an effect significantly blunted by 6 hours incubation with leptin before Aβ₄₂ treatment. Moreover, leptin treatment significantly increased Na⁺/Ca²⁺-exchanger mediated Ca+ transport and current, NCX1 transcript level as well as NCX1 membrane protein abundance. Conclusion: We show that leptin blunts Aβ₄₂-evoked [Ca²⁺]_i increase by increasing expression and activity of Na⁺/Ca²⁺-exchanger NCX1.

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Na+-Ca2+ Exchanger Expression and Its Modulation

Cited by 11 publications

References 43 publications

Sodium-Calcium Exchangers in Rat Trigeminal Ganglion Neurons

Sodium-Calcium Exchangers in Rat Trigeminal Ganglion Neurons

Redox Control of Cardiac Excitability

Effects of Leptin on Na+/Ca2+ Exchanger in PC12 Cells

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