Molecular Cloning and Functional Expression of the Cardiac Sarcolemmal Na
            <sup>+</sup>
            -Ca
            <sup>2+</sup>
            Exchanger

Nicoll, Debora A.; Longoni, S; Philipson, Kenneth D.

doi:10.1126/science.1700476

Cited by 724 publications

(448 citation statements)

References 24 publications

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“…NCX1 recognizes an epitope (residues 393-406) in the large hydrophilic domain between segments 5 and 6 of the Na\Ca exchanger (see Figure 4 for NCX1 epitope localization), a domain supposed to be intracytoplasmic according to the theoretical membrane topology based on hydropathy plot analysis [15], and as confirmed by monoclonal antibody mapping of the canine cardiac Na\Ca exchanger [29]. Accordingly, after treatment of intact reconstituted purified exchanger with Proteinase K, immunodetection of a polypeptide with a molecular mass ranging from approx.…”

Section: Proteolysis Of Intact Reconstituted Purified Na/ca Exchangermentioning

confidence: 99%

“…The Na\Ca exchanger has been cloned and sequenced [15,16] and a theoretical membrane topology was proposed with 11 α-helicoidal membrane-spanning segments, five upstream and six downstream of a large hydrophilic loop comprising more than 50 % of the whole protein. The N-terminus of the canine and bovine 160 and 120 kDa proteins was sequenced and found to be the same N-terminus as the cloned exchanger, starting just after the cleaved signal peptide [11,13].…”

Section: Introductionmentioning

confidence: 99%

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Characterization of the 70 kDa polypeptide of the Na/Ca exchanger

Saba¹,

Bollen²,

Herchuelz³

1999

Biochemical Journal

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The Na/Ca exchanger is associated with 160, 120 and 70 kDa polypeptides whose nature is poorly understood. We have purified and characterized the Na/Ca exchanger from bovine cardiac sarcolemmal vesicles (SLVs) by using ion-exchange and affinity chromatographies. The Na/Ca exchanger-enriched fraction was reconstituted into asolectin liposomes [lipid to protein ratio 10:1 (w/w)] that showed Na/Ca exchange activity. Under non-reducing conditions, SDS/PAGE showed a single 70 kDa polypeptide, which was further characterized by immunoblots with different antibodies: SWant, raised against the purified exchanger protein; NH2-terminus, residues 1–21; NCX1, residues 393–406; and Exon F, residues 622–644. Immunoblots under reducing conditions with SWant, NH2-terminus and NCX1 showed three bands migrating at 160, 120 and 70 kDa for SLV preparations, whereas Exon F reacted only with the 160 and 120 kDa bands. Under non-reducing conditions, immunoblots with purified reconstituted Na/Ca exchanger showed a single band at 70 kDa reacting with SWant, NH2-terminus and NCX1 but not with Exon F. We conclude that the 70 kDa protein is associated with Na/Ca exchange activity, has the same N-terminal sequence as the cloned bovine cardiac exchanger, and has its length decreased by at least 35% from its C-terminal portion as compared with that of the wild-type exchanger.

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Section: Proteolysis Of Intact Reconstituted Purified Na/ca Exchangermentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Characterization of the 70 kDa polypeptide of the Na/Ca exchanger

Saba¹,

Bollen²,

Herchuelz³

1999

Biochemical Journal

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“…Thus, transport of Ca 2+ out of the cell by Na + /Ca 2+ exchange generates inward current. The mammalian nervous system amply expresses three NCX isoforms (Nicoll et al 1990(Nicoll et al , 1996Li et al 1994), and therefore Na + /Ca 2+ exchange currents are expected whenever cytoplasmic Ca 2+ is elevated, including in response to activation of Group I mGlu receptors.…”

Section: Direct Excitatory Effects Of Mglu Receptorsmentioning

confidence: 99%

Control of neuronal excitability by Group I metabotropic glutamate receptors

Amb

Jds

et al. 2017

Biophys Rev

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Metabotropic glutamate (mGlu) receptors couple through G proteins to regulate a large number of cell functions. Eight mGlu receptor isoforms have been cloned and classified into three Groups based on sequence, signal transduction mechanisms and pharmacology. This review will focus on Group I mGlu receptors, comprising the isoforms mGlu 1 and mGlu 5 . Activation of these receptors initiates both G protein-dependent and -independent signal transduction pathways. The G-protein-dependent pathway involves mainly Gα q , which can activate PLCβ, leading initially to the formation of IP 3 and diacylglycerol. IP 3 can release Ca 2+ from cellular stores resulting in activation of Ca 2+ -dependent ion channels. Intracellular Ca 2+ , together with diacylglycerol, activates PKC, which has many protein targets, including ion channels. Thus, activation of the G-protein-dependent pathway affects cellular excitability though several different effectors. In parallel, G protein-independent pathways lead to activation of non-selective cationic currents and metabotropic synaptic currents and potentials. Here, we provide a survey of the membrane transport proteins responsible for these electrical effects of Group I metabotropic glutamate receptors.

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“…Three NCX and five NCKX isoforms have been identified by molecular cloning. NCX1 is predominantly expressed in the heart, brain, and kidney, although it is also present in a broad variety of cell types, whereas NCX2 and 3 expression is limited to brain and skeletal muscle (38,42,43). NCKX1 is exclusively expressed in retinal rod outer segments, whereas NCKX2 is expressed in brain and cone photoreceptors (47,48,59).…”

Section: K + -Dependent and Independent Na + /Ca 2+ Exchangersmentioning

confidence: 99%

K⁺-Dependent Na⁺/Ca²⁺Exchangers: Key Contributors to Ca²⁺Signaling

Visser

Lytton

2007

Physiology

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Ca 2+ acts as a ubiquitous second messenger to control a wide variety of physiological processes by relaying information within mammalian cells (6). For example, Ca 2+ signals trigger fertilization, control development and differentiation, coordinate cellular functions, and even play roles in cell death. The large variety of functional effects are dictated by the spatial and temporal nature of the Ca 2+ signals and by the cellular context in which they occur, that is, the tissue and cell-specific complement of Ca 2+ influx/efflux pathways and downstream targets determine the final outcome. Cytosolic Ca 2+ influx typically occurs when Ca 2+ channels localized to the plasma or endoplasmic reticular membranes open in response to various stimuli such as membrane depolarization or ligand binding (5). Ca 2+ can be subsequently removed from the cytosol by various mechanisms: sarco/endoplasmic reticulum Ca 2+ ATPases (SERCA) and plasma membrane Ca 2+ ATPases (PMCA) utilize the energy from ATP hydrolysis to pump Ca 2+ into the endoplasmic reticulum or outside the cell, respectively, and Na + /Ca 2+ exchangers extrude cytosolic Ca 2+ in exchange for extracellular Na + . In certain cellular contexts, such as localized signals in the dendritic spines of neurons, Ca 2+ flux across the plasma membrane predominates over that from intracellular stores (2, 49). In such cases, PMCA proteins control the resting Ca 2+ concentrations because of their high-affinity/lowcapacity transport properties, whereas Na + /Ca 2+ exchangers display low-affinity/high-capacity transport properties that are ideally suited for cytosolic clearance when Ca 2+ is elevated following a signaling event. Detailed knowledge of the physiological and biochemical properties of calcium channels and transporters is critical to understanding the mechanisms of Ca 2+ signaling in various cellular contexts. This review will focus on recent progress in the understanding of the physiology, function, structure, and regulation of the recently identified family of K + -dependent Na + /Ca 2+ exchangers. K + -Dependent and Independent Na + /Ca 2+ ExchangersThere are two families of Na + /Ca 2+ exchangers in mammalian cells: those that are K + -dependent (NCKX) and those that are K + -independent (NCX). Physiologically, NCX proteins function by extruding cytosolic Ca 2+ in exchange for extracellular Na + ions, whereas NCKX proteins extrude cytosolic Ca 2+ and K + in exchange for Na + ions, which in both cases is referred to as forward mode exchange. In conditions of altered ion gradients and membrane potential, these exchangers can also mediate Ca 2+ entry or so-called reverse mode operation. Three NCX and five NCKX isoforms have been identified by molecular cloning. NCX1 is predominantly expressed in the heart, brain, and kidney, although it is also present in a broad variety of cell types, whereas NCX2 and 3 expression is limited to brain and skeletal muscle (38,42,43). NCKX1 is exclusively expressed in retinal rod outer segments, whereas NCKX2 is expressed in brain and c...

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Molecular Cloning and Functional Expression of the Cardiac Sarcolemmal Na ⁺ -Ca ²⁺ Exchanger

Cited by 724 publications

References 24 publications

Characterization of the 70 kDa polypeptide of the Na/Ca exchanger

Characterization of the 70 kDa polypeptide of the Na/Ca exchanger

Control of neuronal excitability by Group I metabotropic glutamate receptors

K⁺-Dependent Na⁺/Ca²⁺Exchangers: Key Contributors to Ca²⁺Signaling

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Molecular Cloning and Functional Expression of the Cardiac Sarcolemmal Na + -Ca 2+ Exchanger

Cited by 724 publications

References 24 publications

Characterization of the 70 kDa polypeptide of the Na/Ca exchanger

Characterization of the 70 kDa polypeptide of the Na/Ca exchanger

Control of neuronal excitability by Group I metabotropic glutamate receptors

K+-Dependent Na+/Ca2+Exchangers: Key Contributors to Ca2+Signaling

Contact Info

Product

Resources

About

Molecular Cloning and Functional Expression of the Cardiac Sarcolemmal Na ⁺ -Ca ²⁺ Exchanger

K⁺-Dependent Na⁺/Ca²⁺Exchangers: Key Contributors to Ca²⁺Signaling