Connexins regulate calcium signaling by controlling ATP release

Connexins regulate calcium signaling by controlling ATP release
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DOI:
10.1073/pnas.95.26.15735
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发表时间:
1998-12-22
影响因子:
11.1
通讯作者:
Nedergaard, M
Nedergaard, M
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Cotrina, ML;Lin, JHC;Nedergaard, M

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间隙连接蛋白,连接蛋白的强制表达,使间隙连接缺陷细胞系传播细胞间钙波。在这里,我们表明,ATP分泌的耦合不良的细胞系,C6胶质瘤,HeLa细胞,和U373胶质母细胞瘤,是增强连接蛋白表达的5至15倍。ATP释放需要嘌呤受体激活的细胞内Ca 2+动员,并被Cl-通道阻滞剂抑制。钙波的传播也被嘌呤能受体拮抗剂和Cl-通道阻滞剂降低,但对缝隙连接抑制剂不敏感。这些观察结果表明,与连接蛋白表达相关的细胞间信号传导是由ATP释放增强引起的,而不是像以前认为的那样,由细胞间偶联增加引起的。
Forced expression of gap junction proteins, connexins, enables gap junction-deficient cell lines to propagate intercellular calcium waves. Here, we show that ATP secretion from the poorly coupled cell lines, C6 glioma, HeLa, and U373 glioblastoma, is potentiated 5- to 15-fold by connexin expression. ATP release required purinergic receptor-activated intracellular Ca2+ mobilization and was inhibited by Cl- channel blockers. Calcium wave propagation also was reduced by purinergic receptor antagonists and by Cl- chan nel blockers but insensitive to gap junction inhibitors. These observations suggest that cell-to-cell signaling associated with connexin expression results from enhanced ATP release and not, as previously believed, from an increase in intercellular coupling.