Regulation of Ca2+ transport in brain mitochondria. II. The mechanism of the adenine nucleotides enhancement of Ca2+ uptake and retention.
Regulation of Ca2+ transport in brain mitochondria. II. The mechanism of the adenine nucleotides enhancement of Ca2+ uptake and retention.
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脑线粒体 Ca2 运输的调节。
DOI：
10.1016/0005-2728(90)90010-2
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发表时间：
1990
期刊：
影响因子：
--
通讯作者：
Marbach,M
中科院分区：
文献类型：
--
作者：
Rottenberg,H;Marbach,M
ADP 极大地提高了 Ca2+ 的摄取率和 Ca2+ 负载线粒体中的保留率。 ADP/ATP 转运蛋白的特异性抑制剂白术苷完全抑制 ADP 作用，而转运蛋白的另一种特异性抑制剂 bongkrekate 则增强 ADP 的作用。这些结果表明，将 ADP/ATP 易位子锁定在 M 状态足以产生 ADP 效应。环孢素 A 是 Ca2+ 诱导膜透化的特异性抑制剂，不能替代 ADP，表明 ADP 直接影响生电 Ca2+ 摄取速率。易位子构象对生电 Ca2+ 摄取速率的影响与 Pi 的浓度无关，并且不是由膜电位的变化引起的。然而，将载流子锁定在 M 态似乎会增加内膜基质面上的负表面电荷。这可能导致 Ca2+ 从基质表面的生电载体解离的速率提高。通过将载体锁定在 M 状态，不依赖 Na+ 的 Ca2+ 流出速率仅受到轻微抑制，大概是由于相同的机制。在 ADP 存在的情况下，Pi 抑制不依赖 Na+ 的外流。在存在生理浓度的精胺、Pi和Mg2+的情况下，Ca2+摄取速率、Ca2+保留和Ca2+设定点很大程度上取决于ADP生理范围内的ADP浓度。因此，细胞质ADP浓度的变化可能导致线粒体摄取Ca2+的速率发生变化，从而调节细胞质游离钙的兴奋-弛豫循环。
ADP greatly enhances the rate of Ca2+uptake and retention in Ca2+loaded mitochondria. Atractyloside, a specific inhibitor of the ADP/ATP translocator, completely inhibits the ADP effect, while bongkrekate, another specific inhibitor of the translocator enhances the effect of ADP. These results indicate that locking the ADP/ATP translocator in the M-state is sufficient to produce the ADP effect. Cyclosporin A, a specific inhibitor of the Ca2+-induced membrane permeabilization does not substitute for ADP, indicating that ADP directly affect the rate of electrogenic Ca2+uptake. The effect of the translocator conformation on the rate of electrogenic Ca2+uptake is independent of the concentration of Piand is not caused by changes in membrane potential. However, locking the carrier in the M-state appears to increase the negative surface charge on the matrix face of the inner membrane. This may lead to an enhanced rate of Ca2+dissociation from the electrogenic carrier at the matrix surface. The rate of Na+-independent Ca2+efflux is only slightly inhibited by locking the carrier in the M-state, presumably due to the same mechanism. In the presence of ADP, Piinhibits the Na+-independent efflux. In the presence of physiological concentrations of spermine, Piand Mg2+, the rate of Ca2+uptake, Ca2+retention and Ca2+set points depend sharply on ADP concentration at the physiological range of ADP. Thus, changes of cytosolic ADP concentration may lead to change in the rate of Ca2+uptake by mitochondria and thus modulate the excitation-relaxation cycles of cytoplasmic free calcium.