共查询到20条相似文献,搜索用时 31 毫秒
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Marshall CR Pan TC Le HD Omelchenko A Hwang PP Hryshko LV Tibbits GF 《The Journal of biological chemistry》2005,280(32):28903-28911
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PC12 cells were stably transfected with cDNA encoding the Na(+)/Ca(2+) exchanger (NCX1.4). A robust Na(+)-dependent Ca(2+) uptake confirmed the functional expression of the protein. When NCX1. 4 expressing cells (NO) and vector transfected control cells (VC) were exposed to 0.5-20 microM ionomycin for 6 h, a dose-dependent increase in LDH release was observed. LDH release was significantly reduced in NO when compared with VC. When either VC and NO were treated with 3 microM ionomycin and 1.1 mM EGTA, the increase in LDH release was nearly abolished. However, when VC and NO were treated with ionomycin and then EGTA was added 2 min later, LDH release remained elevated. These data suggest ionomycin-induced cell death was Ca(2+) dependent and expressing NCX1.4 may have ameliorated cell death by reducing elevated [Ca(2+)](I). 相似文献
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Zhang XQ Qureshi A Song J Carl LL Tian Q Stahl RC Carey DJ Rothblum LI Cheung JY 《American journal of physiology. Heart and circulatory physiology》2003,284(1):H225-H233
Previous studies have shown that overexpression of phospholemman (PLM) affected contractile function and Ca(2+) homeostasis in adult rat myocytes. We tested the hypothesis that PLM modulated Na(+)/Ca(2+) exchanger (NCX1) activity. PLM was overexpressed in adult rat myocytes by adenovirus-mediated gene transfer. After 72 h, the half-time of relaxation from caffeine-induced contracture, an estimate of forward NCX1 activity, was prolonged 1.8-fold (P < 0.003) in myocytes overexpressing PLM compared with control myocytes overexpressing green fluorescent protein alone. Reverse NCX1 current (3 Na(+) out:1 Ca(2+) in) was significantly (P < 0.0001) lower in PLM myocytes, especially at more positive voltages. Immunofluorescence demonstrated colocalization of PLM and NCX1 to the plasma membrane and t-tubules. Resting membrane potential, action potential amplitude and duration, myocyte size, and NCX1 and calsequestrin protein levels were not affected by PLM overexpression. At 5 mM extracellular [Ca(2+)] ([Ca(2+)](o)), the depressed contraction amplitudes in PLM myocytes were increased towards normal by cooverexpression with NCX1. At 0.6 mM [Ca(2+)](o), the supranormal contraction amplitudes in PLM myocytes were reduced by cooverexpression with NCX1. We conclude that PLM modulated myocyte contractility partly by inhibiting Na(+)/Ca(2+) exchange. 相似文献
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The cardiac Na+-Ca2+ exchanger (NCX1) is a membrane protein that extrudes Ca2+ from cells using the energy of the Na+ gradient and is a key protein in regulating intracellular Ca2+ and contractility. Based on the current topological model, NCX1 consists of nine transmembrane segments (TMSs). The N-terminal five TMSs are separated from the C-terminal four TMSs by a large intracellular loop. Cysteine 768 is modeled to be in TMS 6 close to the intracellular surface. In this study, the proximity of TMS 6 to TMSs 1 and 2 was examined. Insect High Five cells were transfected with cDNAs encoding mutant NCX1 proteins. Each mutant contained cysteine 768 and an introduced cysteine in TMS 1 or 2. Cross-linking between cysteines was determined after reaction with thiol-specific cross-linkers containing spacer arms of 6.5-12 A. The data indicate that residues in TMSs 1 and 2 are close to cysteine 768 in TMS 6. Cysteine 768 cross-linked with residues at both ends of TMSs 1 and 2 and is likely located toward the middle of TMS 6. Based on these results, we present an expanded helix-packing model for NCX1. 相似文献
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Targeted disruption of Na+/Ca2+ exchanger gene leads to cardiomyocyte apoptosis and defects in heartbeat 总被引:3,自引:0,他引:3
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 Komuro I 《The Journal of biological chemistry》2000,275(47):36991-36998
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. 相似文献
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