REGULATION OF BRAIN MITOCHONDRIAL CALCIUM-ION TRANSPORT - ROLE OF ATP IN THE DISCRIMINATION BETWEEN KINETIC AND MEMBRANE-POTENTIAL-DEPENDENT CALCIUM-ION EFFLUX MECHANISMS

REGULATION OF BRAIN MITOCHONDRIAL CALCIUM-ION TRANSPORT - ROLE OF ATP IN THE DISCRIMINATION BETWEEN KINETIC AND MEMBRANE-POTENTIAL-DEPENDENT CALCIUM-ION EFFLUX MECHANISMS
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DOI:
10.1042/bj1860833
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发表时间:
1980-01-01
影响因子:
4.1
通讯作者:
SCOTT, ID
SCOTT, ID
中科院分区:
生物学3区
文献类型:
--
作者:
NICHOLLS, DG;SCOTT, ID

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从豚鼠大脑皮层的线粒体孵育在Pi或醋酸盐的存在下是无法调节的extramoditrial游离Ca 2+在一个稳定的状态,这是独立的Ca 2+在基质中积累。这是由于叠加的动力学调节的钙离子循环的膜电位依赖性逆转的钙离子单向转运体。后一种外排是低膜电位的结果,这与基质中腺嘌呤核苷酸的丢失相关。低浓度的ATP防止腺嘌呤核苷酸从基质中丢失,使线粒体能够保持高的膜电位,并允许线粒体在基质中积累高达200 nmol Ca 2 +/mg蛋白质时精确地缓冲线粒体外游离Ca 2+。稳定状态的线粒体外游离Ca 2+保持低至0.3 μ M。Na+激活的外排途径在ATP和寡霉素的存在下是功能性的,并且精确地解释了由Na+添加诱导的稳态游离Ca 2+的变化。需要仔细区分动力学和膜电位依赖性外排途径的强调和脑线粒体的能力,以调节胞质游离钙离子浓度在体内进行了讨论。
Mitochondria from guinea-pig cerebral cortex incubated in the presence of Pi or acetate are unable to regulate the extramitochondrial free Ca2+ at a steady-state which is independent of the Ca2+ accumulated in the matrix. This is due to the superimposition on kinetically regulated Ca2+ cycling of a membrane-potential-dependent reversal of the Ca2+ uniporter. The latter efflux is a consequence of a low membrane potential, which correlates with a loss of adenine nucleotides from the matrix. Low concentrations of ATP prevent adenine nucleotide loss from the matrix enable the mitochondria to maintain a high membrane potential and allow the mitochondria to buffer the extramitochondrial free Ca2+ precisely when up to 200 nmol of Ca2+/mg of protein is accumulated in the matrix. The steady-state extramitochondrial free Ca2+ is maintained as low as 0.3 .mu.M. The Na+-activated efflux pathway is functional in the presence of ATP and oligomycin and accounts precisely for the change in steady-state free Ca2+ induced by Na+ addition. The need to distinguish carefully between kinetic and membrane-potential-dependent efflux pathways is emphasized and the competence of brain mitochondria to regulate cytosolic free Ca2+ concentrations in vivo is discussed.