Coordinated intercellular calcium waves induced by noradrenaline in rat hepatocytes: dual control by gap junction permeability and agonist

Coordinated intercellular calcium waves induced by noradrenaline in rat hepatocytes: dual control by gap junction permeability and agonist
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大鼠肝细胞去甲肾上腺素诱导的协调细胞间钙波:间隙连接通透性和激动剂的双重控制

DOI:
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发表时间:
1997
期刊:
影响因子:
11.4
通讯作者:
L. Combettes
L. Combettes
中科院分区:
生物学1区
文献类型:
--
作者:
T. Tordjmann;B. Berthon;M. Claret;L. Combettes

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钙动员激动剂诱导细胞内Ca 2+浓度([Ca 2 +]i)变化,被认为是触发细胞反应。在连接的细胞中,[Ca 2 +]i的升高可以作为细胞间Ca 2+波在细胞间传播,其机制尚未阐明。使用负载fura 2的大鼠肝细胞,我们研究了控制去甲肾上腺素诱导的Ca 2+信号的协调和细胞间传播的机制。用18 α-大黄酸阻断缝隙连接导致连接细胞之间失去协调。我们发现,第二信使和[Ca 2 +]i上升,在一个肝细胞不能触发Ca 2+反应连接的细胞,这表明跨间隙连接的扩散,而需要协调,是不足以本身的细胞间Ca 2+波的传播。此外,我们的实验揭示了连接的肝细胞中去甲肾上腺素诱导的Ca 2+信号之间的功能差异。这些结果表明,在大鼠肝细胞的多细胞系统的细胞间Ca 2+信号的传播和高度组织通过复杂的机制,涉及至少三个因素。首先,间隙连接偶联确保了不同细胞之间[Ca 2 +]i振荡的协调;其次,每个肝细胞中激素的存在是细胞间Ca 2+信号传播所必需的;第三,相邻连接的肝细胞之间的功能差异可能允许Ca 2+波的“起搏器样”细胞间传播。
Calcium‐mobilizing agonists induce intracellular Ca2+ concentration ([Ca2+]i) changes thought to trigger cellular responses. In connected cells, rises in [Ca2+]i can propagate from cell to cell as intercellular Ca2+ waves, the mechanisms of which are not elucidated. Using fura2‐loaded rat hepatocytes, we studied the mechanisms controlling coordination and intercellular propagation of noradrenaline‐induced Ca2+ signals. Gap junction blockade with 18 α‐glycyrrhetinic acid resulted in a loss of coordination between connected cells. We found that second messengers and [Ca2+]i rises in one hepatocyte cannot trigger Ca2+ responses in connected cells, suggesting that diffusion across gap junctions, while required for coordination, is not sufficient by itself for the propagation of intercellular Ca2+ waves. In addition, our experiments revealed functional differences between noradrenaline‐induced Ca2+ signals in connected hepatocytes. These results demonstrate that intercellular Ca2+ signals in multicellular systems of rat hepatocytes are propagated and highly organized through complex mechanisms involving at least three factors. First, gap junction coupling ensures coordination of [Ca2+]i oscillations between the different cells; second, the presence of hormone at each hepatocyte is required for cell‐cell Ca2+ signal propagation; and third, functional differences between adjacent connected hepatocytes could allow a ‘pacemaker‐like’ intercellular spread of Ca2+ waves.
间隙连接通讯调节胰腺腺泡中的 [Ca2]i 振荡和酶分泌。
DOI: --
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