Functional linkage of Na+-Ca2+-exchanger to sarco/endoplasmic reticulum Ca2+pump in coronary artery: comparison of smooth muscle and endothelial cells

Functional linkage of Na+-Ca2+-exchanger to sarco/endoplasmic reticulum Ca2+pump in coronary artery: comparison of smooth muscle and endothelial cells
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DOI:
10.1111/j.1582-4934.2008.00480.x
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发表时间:
2009-08-01
影响因子:
5.3
通讯作者:
Grover, Ashok K.
Grover, Ashok K.
中科院分区:
医学2区
文献类型:
--
作者:
Davis, Kim A.;Samson, Sue E.;Grover, Ashok K.

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冠状动脉平滑肌细胞内Ca ~(2+)浓度的增加引起收缩,而内皮细胞内Ca ~(2+)浓度的增加引起舒张。Na+-Ca ~(2+)-交换器(NCX)可能在两种细胞类型的Ca ~(2+)动态中起作用。在此,在Na+负载的猪冠状动脉平滑肌和内皮细胞中比较了NCX介导的45 Ca 2+摄取。在这两种细胞类型中,这种摄取被KB-R7943、SEA 0400和莫能菌素抑制,但不被cariporide抑制。预先用Ca 2+螯合剂BAPTA加载细胞增加了平滑肌中但不是内皮细胞中的NCX介导的45 Ca 2+摄取。在存在或不存在BAPTA负载的情况下,Na+介导的45 Ca 2+摄取在内皮细胞中比在平滑肌细胞中更大。在没有BAPTA负载的平滑肌细胞中,毒胡萝卜素减少了NCX介导的45 Ca 2+进入。在BAPTA加载后,在内皮细胞或任一细胞类型中均未观察到这种效应。平滑肌细胞中的结果与有限扩散空间模型一致,其中通过胞质Ca 2+的螯合或通过肌浆网/内质网Ca 2+泵(SERCA)的螯合来增强NCX介导的45 Ca 2+摄取。它们表明NCX和SERCA在平滑肌中而不是在内皮细胞中存在功能联系。NCX和SERCA之间的联系在平滑肌的概念也证实了类似的分布NCX和SERCA 2蛋白质时,洗涤剂处理的微粒体通过浮选蔗糖密度梯度分级。因此,冠状动脉平滑肌和内皮细胞不仅在NCX的相对活性上不同,而且在其与SERCA的功能联系上也不同。
An increase in cytosolic Ca2+ concentration in coronary artery smooth muscle causes a contraction but in endothelium it causes relaxation. Na+-Ca2+-exchanger (NCX) may play a role in Ca2+ dynamics in both the cell types. Here, the NCX-mediated 45Ca2+ uptake was compared in Na+-loaded pig coronary artery smooth muscle and endothelial cells. In both the cell types, this uptake was inhibited by KB-R7943, SEA 0400 and by monensin, but not by cariporide. Prior loading of the cells with the Ca2+ chelator BAPTA increased the NCX-mediated 45Ca2+ uptake in smooth muscle but not in endothelial cells. In the presence or absence of BAPTA loading, the Na+-mediated 45Ca2+ uptake was greater in endothelial than in smooth muscle cells. In smooth muscle cells without BAPTA loading, thapsigargin diminished the NCX-mediated 45Ca2+ entry. This effect was not observed in endothelial cells or in either cell type after BAPTA loading. The results in the smooth muscle cells are consistent with a limited diffusional space model in which the NCX-mediated 45Ca2+ uptake was enhanced by chelation of cytosolic Ca2+ or by its sequestration by the sarco/endoplasmic reticulum Ca2+ pump (SERCA). They suggest a functional linkage between NCX and SERCA in the smooth muscle but not in the endothelial cells. The concept of a linkage between NCX and SERCA in smooth muscle was also confirmed by similar distribution of NCX and SERCA2 proteins when detergent-treated microsomes were fractionated by flotation on sucrose density gradients. Thus, the coronary artery smooth muscle and endothelial cells differ not only in the relative activities of NCX but also in its functional linkage to SERCA.