In cardiac myocytes, Ca(2+) concentrations alternate between high levels during contraction and low levels during relaxation. The increase in Ca(2+) concentration during contraction is primarily due to release of Ca(2+) from intracellular stores. However, some Ca(2+) also enters the cell through the sarcolemma (plasma membrane). During relaxation, Ca(2+) is sequestered within the intracellular stores. To prevent overloading of intracellular stores, the Ca(2+) that entered across the sarcolemma must be extruded from the cell. The Na(+)-Ca(2+) exchanger is the primary mechanism by which the Ca(2+) is extruded from the cell during relaxation. The amino acid sequence of this exchanger does not resemble that of any previously described protein. In the heart, the exchanger may play a key role in digitalis action. The exchanger is the dominant mechanism in returning the cardiac myocyte to its resting state following excitation.
General function
Channel/transport protein
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Cellular localization
Plasma membrane
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Ovarian function
Oogenesis
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Role of Na+/Ca2+ Exchanger (NCX) in Modulating Postovulatory Aging of Mouse and Rat Oocytes. Zhang CX 2014 et al.
We studied the role of the Na+/Ca2+ exchanger (NCX) in modulating oocyte postovulatory aging by observing changes in NCX contents and activities in aging mouse and rat oocytes. Whereas the NCX activity was measured by observing oocyte activation following culture with NCX inhibitor or activator, the NCX contents were determined by immunohistochemical quantification. Although NCX was active in freshly-ovulated rat oocytes recovered 13 h post hCG injection and in aged oocytes recovered 19 h post hCG in both species, it was not active in freshly-ovulated mouse oocytes. However, NCX became active when the freshly-ovulated mouse oocytes were activated with ethanol before culture. Measurement of cytoplasmic Ca2+ revealed Ca2+ increases always before NCX activation. Whereas levels of the reactive oxygen species (ROS) and the activation susceptibility increased, the density of NCX member 1 (NCX1) decreased significantly with oocyte aging in both species. While culture with H2O2 decreased the density of NCX1 significantly, culture with NaCl supplementation sustained the NCX1 density in mouse oocytes. It was concluded that (a) the NCX activity was involved in the modulation of oocyte aging and spontaneous activation; (b) ROS and Na+ regulated the NCX activity in aging oocytes by altering its density as well as functioning; and (c) cytoplasmic Ca2+ elevation was essential for NCX activation in the oocyte.
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Expression regulated by
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Ovarian localization
Oocyte
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Zolt?Mach? et al 2002 reported the expression of Na+/Ca2+ Exchanger in Porcine Oocytes.
The presence of the Na+/Ca2+ exchange mechanism was investigated in porcine oocytes. Immature and in vitro-matured oocytes were loaded with the Ca2+-sensitive fluorescent dye fura 2 and changes in the intracellular free Ca2+ concentration ([Ca2+]i) were monitored after altering the Na+ concentration gradient across the plasma membrane. Decreasing the extracellular Na+ concentration induced an increase in [Ca2+]i possibly by a Ca2+ influx via the Na+/Ca2+ exchanger. A similar Ca2+ influx could also be triggered after increasing the intracellular Na+ concentration by incubation in the presence of ouabain (0.4 mM), a Na+/K+-ATPase inhibitor. The increase in the [Ca2+]i was due to Ca2+ influx since it was abolished in the absence of extracellular Ca2+, and the increase was mediated by the Na+/Ca2+ exchanger since it was blocked by the application of amiloride or bepridil, inhibitors of Na+/Ca2+ exchange. Verapamil (50 ?M) and pimozide (50 ?M), inhibitors of L- and T-type voltage-gated Ca2+ channels, respectively, could not block the Ca2+ influx. The Ca2+ entry via the Na+/Ca2+ exchanger could not induce the release of cortical granules and did not stimulate the resumption of meiosis. This was unexpected because Ca2+ is thought to be a universal trigger for activation. Using antibodies raised against the exchanger, it was demonstrated that the Na+/Ca2+ exchanger was localized predominantly in the plasma membrane. Reverse transcription-polymerase chain reaction revealed that porcine oocytes contain a transcript that shows 98.1% homology to the NACA3 isoform of the porcine Na+/Ca2+ exchanger.