生物谷报道： 线粒体对钙的吸收是首次于1961年观察到的，被认为是通过一个Uniporter进行的。一个Uniporter是一种膜蛋白，调节目标离子的运输，而又不将这种运输与任何其他分子或离子的运输联系起来。钙的Uniporter在线粒体中扮演着一个非常重要的角色，使Ca2+具有高渗透性，而使K+无法渗透，即便在胞质中Ca2+水平很低时也是如此。但Uniporter却难以纯化或克隆，它是一种载体还是一种通道也一直不清楚。现在，Kirichok等人识别出一种新颖的钙通道，它所具有的性质与人们长期寻找的钙的Uniporter的性质一致。穿过线粒体内膜的电流是在整个线粒质（没有外层膜的线粒体）中测定的。这一假定的钙Uniporter在非常低的负电势下打开，这使得Ca2+可有效运输进激发的线粒体中。
Nature 427, 360 - 364 (22 January 2004); doi:10.1038/nature02246
The mitochondrial calcium uniporter is a highly selective ion channel
YURIY KIRICHOK, GRIGORY KRAPIVINSKY & DAVID E. CLAPHAM
Howard Hughes Medical Institute, Department of Cardiovascular Research, Children's Hospital, and Department of Neurobiology, Harvard Medical School, 320 Longwood Avenue, Boston, Massachusetts 02115, USA
Correspondence and requests for materials should be addressed to D.E.C. (dclapham@enders.tch.harvard.edu).
During intracellular Ca2+ signalling mitochondria accumulate significant amounts of Ca2+ from the cytosol1, 2. Mitochondrial Ca2+ uptake controls the rate of energy production1, 3, 4, shapes the amplitude and spatio-temporal patterns of intracellular Ca2+ signals1, 5-8, and is instrumental to cell death9, 10. This Ca2+ uptake is undertaken by the mitochondrial Ca2+ uniporter (MCU) located in the organelle's inner membrane11, 12. The uniporter passes Ca2+ down the electrochemical gradient maintained across this membrane without direct coupling to ATP hydrolysis or transport of other ions11. Carriers are characterized by turnover numbers that are typically 1,000-fold lower than ion channels, and until now it has been unclear whether the MCU is a carrier or a channel13. By patch-clamping the inner mitochondrial membrane, we identified a previously unknown Ca2+-selective ion channel sensitive to inhibitors of mitochondrial Ca2+ uptake. Our data indicate that this unique channel binds Ca2+ with extremely high affinity (dissociation constant 2 nM), enabling high Ca2+ selectivity despite relatively low cytoplasmic Ca2+ concentrations. The channel is inwardly rectifying, making it especially effective for Ca2+ uptake into energized mitochondria. Thus, we conclude that the properties of the current mediated by this novel channel are those of the MCU.
