Role of sodium in mitochondrial membrane depolarization induced by P2X7 receptor activation in submandibular glands
Role of sodium in mitochondrial membrane depolarization induced by P2X7 receptor activation in submandibular glands
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DOI：
10.1016/j.febslet.2005.08.074
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发表时间：
2005-10-10
期刊：
影响因子：
3.5
通讯作者：
Marino, A
中科院分区：
文献类型：
--
作者：
Garcia-Marcos, M;Fontanils, U;Marino, A
研究了ATP对大鼠下颌下腺线粒体膜去极化的影响。细胞悬液暴露于高浓度ATP诱导线粒体膜持续去极化。这种作用在镁存在下被阻断，并被低浓度的2 '，3'-O-（4-苯甲酰基苯甲酰基）腺苷5 '-三磷酸（BzATP）复制，表明P2 X（7）嘌呤能受体的作用。这一点通过比较野生型和P2 X（7）敲除（P2 X（7）R（-/-））小鼠对ATP的反应得到证实。线粒体在ATP刺激后吸收钙，但ATP对线粒体膜的去极化不受细胞外介质中钙的去除的影响。在不存在钠的情况下几乎完全抑制，并被线粒体Na/Ca交换抑制剂7-氯-5-（2-氯苯基）-1，5-二氢-4，1-苯并硫氮杂卓-2（3 H）-酮（CGP-37157）部分阻断。ATP和莫能菌素均能增加细胞外钠离子的摄取（如质膜的去极化所示），但钠离子载体不影响线粒体膜电位，因此认为P2 X（7）受体的激活使线粒体膜去极化。细胞外钠的摄取是必要的，但不足以诱导这种反应。(c)2005年欧洲生物化学学会联合会。Elsevier B. V.出版，保留所有权利。
The effect of ATP on mitochondrial membrane depolarization in rat submandibular glands was investigated. Exposure of the cell suspension to high concentrations of ATP induced a sustained depolarization of mitochondrial membrane. This effect was blocked in the presence of magnesium and reproduced by low concentrations of 2',3'-O-(4-benzoylbenzoyl)adenosine 5'-triphosphate (BzATP), suggesting the implication of the P2X(7) purinergic receptor. This point was confirmed by comparison of the response to ATP by wild-type and P2X(7) knock-out (P2X(7)R(-/-)) mice. Mitochondria took up calcium after ATP stimulation but the depolarization of the mitochondrial membrane by ATP was not affected by the removal of calcium from the extracellular medium. It was nearly fully suppressed in the absence of sodium and partially blocked by the mitochondrial Na/Ca exchanger inhibitor 7-chloro-5-(2-chlorophenyl)-1,5-dihydro-4,1-benzothiazepin-2(3H)-one (CGP-37157). Both ATP and monensin increased the uptake of extracellular sodium (as shown by the depolarization of the plasma membrane) but the sodium ionophore did not affect the mitochondrial membrane potential.It is concluded that the activation of P2X(7) receptors depolarizes the mitochondrial membrane. The uptake of extracellular sodium is necessary but not sufficient to induce this response. (c) 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.