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Mediates the exchange of one Ca(2+) ion against three to four Na(+) ions across the cell membrane, and thereby contributes to the regulation of cytoplasmic Ca(2+) levels and Ca(2+)-dependent cellular processes. Contributes to Ca(2+) transport during excitation-contraction coupling in muscle. In a first phase, voltage-gated channels mediate the rapid increase of cytoplasmic Ca(2+) levels due to release of Ca(2+) stores from the endoplasmic reticulum. SLC8A1 mediates the export of Ca(2+) from the cell during the next phase, so that cytoplasmic Ca(2+) levels rapidly return to baseline. Required for normal embryonic heart development and the onset of heart contractions.
基因功能參考文獻(xiàn):
The results show that estrogen upregulates cardiac L-type Ca(2+) and sodium-calcium exchange in women through genomic mechanisms that account for sex differences in Ca(2+) handling and spatial heterogeneities of repolarization due to base-apex heterogeneities of Cav1.2alpha and NCX1. By analogy with rabbit studies, these effects account for human sex-difference in arrhythmia risk. PMID: 28807015
Diacylglycerol generation downstream of VEGF receptors activatesTRPC3 causing Na(+) influx with subsequent reversal of NCX1, ERK1/2 activation and ultimately contributes to enhanced angiogenesis. PMID: 28535874
NCX1 expression correlates with the smoking status of esophageal squamous cell carcinoma patients, and NNK activates the Ca2+ entry mode of NCX1 in ESCC cells, leading to cell proliferation and migration PMID: 27588478
We also observed that acetylcholine attenuated the formation of NCX1-TRPC3-IP3R1 complexes and maintained calcium homeostasis in cells treated with TNF-alpha. PMID: 28395930
SLC8A1 polymorphisms alter calcium flux in cells that mediate coronary artery damage in Kawasaki disease. PMID: 27879314
CaSR exerts a suppressive function in pancreatic tumorigenesis through a novel NCX1/Ca(2+)/beta-catenin signaling pathway. PMID: 27108064
Palmitoylation of cardiac NCX1 can modify its function, physical interactions, and removal from the sarcolemma by domain-dependent endocytosis. PMID: 26418268
NCX1 and the calcium binding protein calretinin cooperate within the striatum to confer tolerance against cerebral ischemia. PMID: 25633096
ADD2 and NCX1 variants influence the risk and the clinical features of systemic lupus erythematosus and lupus nephritis. PMID: 26045217
NCX1 operating in reverse mode plays a prominent role in calcium cytosolic regulation in highly metastatic melanoma cells. PMID: 26567603
The expression of miR-206 by HUVECs reduced exosome production by regulating ADP-Ribosylation Factor 6 (ARF6) and sodium/calcium exchanger 1 (NCX1). PMID: 27031991
interaction of NHE1, NCX1 and CaM mediates the effects of IL6 on human hepatocellular carcinoma PMID: 26775040
NCX1.3 is the predominant NCX variant in the distal convoluted and connecting tubules tubules PMID: 26418956
results demonstrate that CaM senses changes in [Ca2+]i and binds to the cytoplasmic loop of NCX1 to regulate exchange activity. PMID: 26421717
The expressions of NCX1 and NCKX4 were significantly higher in the patent ductus arteriosus group at both the protein and mRNA levels. PMID: 25500693
Down-regulation of the SLC8A1 gene, most likely mediated by its regulator miR-223, can lead to decreased calcium in penile carcinoma and consequently to suppressed apoptosis and increased tumor cell proliferation PMID: 25481039
These data confirm the role of NCX1 activity in regulating renal epithelial cell migration. PMID: 25770213
Three novel loci were identified in East Asians with cardiac arrhythmias: rs2483280 (PRDM16 locus) and rs335206 (PRDM6 locus) were associated with QRS duration; and rs17026156 (SLC8A1 locus) correlated with PR interval. PMID: 25035420
There is a functional role of sodium-calcium exchanger SLC8A1 in human atrial and atrioventricular nodal conduction as suggested by genetically modified mouse models. PMID: 25055868
human osteoblasts and osteoblasts from Ano6(-/-) and WT mice, we demonstrate that NCX1 requires Ano6 to efficiently translocate Ca(2+) out of osteoblasts into the calcifying bone matrix PMID: 25589784
CAPN1 anchors to two NCX1 regions and cleaves at methionine-369, leading to NCX1 inactivation in heart failure. PMID: 25336645
Results indicate that levosimendan inhibited reverse-mode Na(+)/Ca(2+) exchanger (NCX) activity to protect cardiomyocyte progenitor cells (CPC)-derived cardiomyocytes from anoxia-reoxygenation (A/R)-induced ER stress and cell death. PMID: 24498266
NCX1 (and EAAT1) are both involved in glutamate-induced ATP synthesis, with NCX1 playing a pivotal role. PMID: 23913256
Biochemical support for a model of NCX1 with 10 transmembrane domains as found in the prokaryotic homologue. PMID: 23376057
Functional and structural properties of the NCKX2 Na(+)-Ca (2+)/K (+) exchanger: a comparison with the NCX1 Na (+)/Ca (2+) exchanger. PMID: 23224872
the transcriptional network regulating Ncx1 expression is also mediating many of the other changes in genetic remodeling contributing to the development of cardiac dysfunction PMID: 23224875
NCX1 and NCX3 -represent two promising druggable targets for setting on new strategies in stroke therapy. PMID: 23224883
human macrophages and monocytes express NCX1 and NCX3 that operate in a bidirectional manner to restore [Ca(2+)](i) to generate Ca(2+) signals and to induce TNF-alpha production. PMID: 23224891
NCX1 is a key component of certain distinct signaling pathways that activate VSM contraction in response to stretch (i.e., myogenic response) and to activation of certain G-protein-coupled receptors. PMID: 23224892
Ncx1 expression is required for increasing sinus rates and in isolated sinoatrial cells. PMID: 23192947
alpha(2)-Na(+) pumps, NCX1, receptor-operated channels, and the sarcoplasmic reticulum regulate Ca(2+) homeostasis and signaling in human arterial smooth muscle cells. PMID: 22842068
this study validated the association between a SNP, rs13017846, which maps to near SLC8A1 (sodium/calcium exchanger 1 precursor, overall p = 8.0 x 10(-14)), and the QT interval. PMID: 22726844
There were no differences of gene frequency between Alzheimer disease cases and controls for any of three polymorphisms of NCX1 gene. However, among AD patients whose age at onset (AAO) was >65 years, carriers of a 14 bp insertion showed a lower AAO. PMID: 21833492
NCX1 is upregulated in chronic atrial fibrillation. A larger I(NCX) for a given SR Ca(2+) release contributes to AF-promoting atrial delayed afterdepolarizations/triggered activity in cAF patients. PMID: 22456474
Human platelets express K(+) -independent Na(+) /Ca(2+) exchangers NCX1.3, NCX3.2 and NCX3.4. PMID: 21790537
a novel function for NHE1 and NCX1 in membrane blebbing and permeability, and establish a link between membrane blebbing and integrin signaling. PMID: 22270364
an essential component in the mechanism governing cardiac steroid-induced slow Ca(2+) oscillations PMID: 21930298
an increase in the NCX1 mRNA due to the apoptosis induction is not regulated by HIF-1alpha PMID: 21613675
Immunohistochemical analysis revealed thatNCKX3 and NCX1 were abundantly localized in the cytoplasm of luminal and glandular epithelial uterine cells throughout the menstrual cycle. NCX1 expression was not affected by estradiol and progesterone. PMID: 21321244
Taken together, these data demonstrate a potentially important role for NCX1 in control of Ca2+ homeostasis and link store depletion via STIM1 directly with NCX activation. PMID: 21126331
NCX1 protein expression in urinary bladder smooth muscle increases approximately 4-fold in NCX1.3 transgenic mice compared to that in wild-type. PMID: 20173311
These results suggest that recovery from intracellular acidosis causes a transient increase in cytosolic Ca(2+) due to reversal of Ca(2+) transport via Na(+)/Ca(2+) exchanger coactivated with Na(+)/H(+) exchanger, which can cause cell death. PMID: 19830548
characterization of NCX1 intronic hypervariable non-coding region enriched in human-specific indel variants PMID: 20109173
Results show that the Na(+)/Ca(2+) exchanger NCLX is enriched in mitochondria, where it is localized to the cristae. PMID: 20018762
data are consistent with a stoichiometry for the NCX1.1 protein of 4 Na+ to 1 Ca2+ to 2 charges moved per transport cycle PMID: 11916852
Na/Ca exchanger overexpression, by depleting ER Ca(2+) stores, triggers the activation of caspase-12 and increases apoptotic cell death PMID: 12031969
Characterization and functional activity of a truncated Na/Ca exchange isoform resulting from a new splicing pattern PMID: 12502539
functional and physical interaction of nonselective TRPC cation channels with NCX proteins as a novel principle of TRPC-mediated Ca(2+) signaling. PMID: 14736881
collagen-induced increase in [Ca2+](i) in platelets is dependent on concentration of Na+ in the extracellular milieu: the collagen-induced increase in [Ca2+](i) causes reversal of the NCX, resulting in an increase in [Ca2+](i) and platelet aggregation PMID: 14981087
Detected primarily in heart and at lower levels in brain. Expressed in cardiac sarcolemma, brain, kidney, liver, pancreas, skeletal muscle, placenta and lung.