PMID:10967099

Citation	Wakimoto, K, Kobayashi, K, Kuro-O, M, Yao, A, Iwamoto, T, Yanaka, N, Kita, S, Nishida, A, Azuma, S, Toyoda, Y, Omori, K, Imahie, H, Oka, T, Kudoh, S, Kohmoto, O, Yazaki, Y, Shigekawa, M, Imai, Y, Nabeshima, Y and Komuro, I (2000) Targeted disruption of Na+/Ca2+ exchanger gene leads to cardiomyocyte apoptosis and defects in heartbeat. J. Biol. Chem. 275:36991-8
Abstract	Ca(2+), which enters cardiac myocytes through voltage-dependent Ca(2+) channels during excitation, is extruded from myocytes primarily by the Na(+)/Ca(2+) exchanger (NCX1) during relaxation. The increase in intracellular Ca(2+) concentration in myocytes by digitalis treatment and after ischemia/reperfusion is also thought to result from the reverse mode of the Na(+)/Ca(2+) exchange mechanism. However, the precise roles of the NCX1 are still unclear because of the lack of its specific inhibitors. We generated Ncx1-deficient mice by gene targeting to determine the in vivo function of the exchanger. Homozygous Ncx1-deficient mice died between embryonic days 9 and 10. Their hearts did not beat, and cardiac myocytes showed apoptosis. No forward mode or reverse mode of the Na(+)/Ca(2+) exchange activity was detected in null mutant hearts. The Na(+)-dependent Ca(2+) exchange activity as well as protein content of NCX1 were decreased by approximately 50% in the heart, kidney, aorta, and smooth muscle cells of the heterozygous mice, and tension development of the aortic ring in Na(+)-free solution was markedly impaired in heterozygous mice. These findings suggest that NCX1 is required for heartbeats and survival of cardiac myocytes in embryos and plays critical roles in Na(+)-dependent Ca(2+) handling in the heart and aorta.
Links	PubMed Online version:10.1074/jbc.M004035200
Keywords	Animals; Antigens, CD31/chemistry; Antigens, CD31/metabolism; Apoptosis; Arrhythmias, Cardiac/genetics; Exons; Heart/physiology; In Situ Hybridization; Mice; Mice, Mutant Strains; Myocardium/cytology; Placenta/chemistry; Sodium-Calcium Exchanger/genetics; Sodium-Calcium Exchanger/physiology; Yolk Sac/chemistry
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:NAC1	involved_in	GO:0098719: sodium ion import across plasma membrane	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:NAC1	involved_in	GO:0044557: relaxation of smooth muscle	ECO:0000315: mutant phenotype evidence used in manual assertion		P	occurs_in:(UBERON:0004178)	Seeded From UniProt	complete
MOUSE:NAC1	enables	GO:0005432: calcium:sodium antiporter activity	ECO:0000315: mutant phenotype evidence used in manual assertion		F	occurs_in:(UBERON:0000948)	Seeded From UniProt	complete
MOUSE:NAC1	involved_in	GO:1901660: calcium ion export	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:NAC1	involved_in	GO:0051481: negative regulation of cytosolic calcium ion concentration	ECO:0000315: mutant phenotype evidence used in manual assertion		P	occurs_in:(UBERON:0000948)	Seeded From UniProt	complete
MOUSE:NAC1	involved_in	GO:0014829: vascular associated smooth muscle contraction	ECO:0000315: mutant phenotype evidence used in manual assertion		P	occurs_in:(UBERON:0004178)	Seeded From UniProt	complete
MOUSE:NAC1	involved_in	GO:0055013: cardiac muscle cell development	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:NAC1	involved_in	GO:0055074: calcium ion homeostasis	ECO:0000315: mutant phenotype evidence used in manual assertion		P	occurs_in:(UBERON:0000948)	Seeded From UniProt	complete
MOUSE:NAC1	involved_in	GO:0060402: calcium ion transport into cytosol	ECO:0000315: mutant phenotype evidence used in manual assertion		P	occurs_in:(UBERON:0000948)	Seeded From UniProt	complete
MOUSE:NAC1	involved_in	GO:0070509: calcium ion import	ECO:0000315: mutant phenotype evidence used in manual assertion		P	occurs_in:(UBERON:0000948)	Seeded From UniProt	complete
MOUSE:NAC1	involved_in	GO:0036376: sodium ion export across plasma membrane	ECO:0000315: mutant phenotype evidence used in manual assertion		P	occurs_in:(UBERON:0000948)	Seeded From UniProt	complete
MOUSE:NAC1	involved_in	GO:0071313: cellular response to caffeine	ECO:0000315: mutant phenotype evidence used in manual assertion		P	occurs_in:(UBERON:0000948)	Seeded From UniProt	complete
MOUSE:NAC1	involved_in	GO:0002027: regulation of heart rate	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete

References

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