Fraser C L, Sarnacki P, Arieff A I
J Clin Invest. 1985 Nov;76(5):1789-95. doi: 10.1172/JCI112170.
Brain calcium is elevated in patients and laboratory animals with uremia. The significance of this finding is unclear. We evaluated calcium transport in brain of both normal and acutely uremic rats (blood urea nitrogen = 250 mg/dl) by performing studies in synaptosomes from rat brain cerebral cortex. Synaptosomes are vesicular presynaptic nerve endings from brain that contain mitochondria and are metabolically active. Two mechanisms of calcium transport were evaluated using radioactive 45Ca++ as a tracer. Both mechanisms were evaluated in the absence of exogenously administered parathyroid hormone (PTH). We first evaluated Na+-Ca++ exchange in vesicles that were loaded with NaCl in an external media containing 10 microM CaCl2. Both initial rates of calcium transport and equilibrium levels of calcium accumulation in synaptosomes prepared from uremic rats were significantly greater (P less than 0.005) than in normal. To assess calcium efflux, ATP-dependent calcium uptake (1 mM ATP) was studied in inverted plasma membrane vesicles loaded with KCl. In the uremic synaptosomes, a significant increase (P less than 0.005) in ATP-dependent calcium uptake was observed as compared with the normal. These studies show that (a) Calcium accumulation via the Na+-Ca++ exchanger is increased in synaptosomes prepared from uremic rat brain. (b) Calcium influx into inverted plasma membrane vesicles from uremic rats via the ATP-dependent calcium transport mechanism is increased when compared with normal. (c) The increased calcium accumulation in uremia by both Na+-Ca++ exchange and ATP-dependent calcium transport mechanism appears to be a result of increased synaptosomal membrane permeability to calcium. Both these abnormalities of calcium transport in uremia would tend to increase brain extracellular calcium in vivo. The defects observed in uremia do not appear to be readily reversible, and the relationship to PTH is presently unclear. These abnormalities may affect neurotransmission in the uremic state.
在患有尿毒症的患者和实验动物中，脑钙水平会升高。这一发现的意义尚不清楚。我们通过对大鼠脑皮质突触体进行研究，评估了正常大鼠和急性尿毒症大鼠（血尿素氮 = 250 mg/dl）脑中的钙转运情况。突触体是来自大脑的含有线粒体且具有代谢活性的囊泡状突触前神经末梢。使用放射性45Ca++作为示踪剂评估了两种钙转运机制。两种机制均在未外源性给予甲状旁腺激素（PTH）的情况下进行评估。我们首先在含有10 microM CaCl2的外部介质中，评估了装载有NaCl的囊泡中的Na+-Ca++交换。与正常大鼠制备的突触体相比，尿毒症大鼠制备的突触体中钙转运的初始速率和钙积累的平衡水平均显著更高（P < 0.005）。为了评估钙外流，在装载有KCl的倒置质膜囊泡中研究了ATP依赖性钙摄取（1 mM ATP）。与正常情况相比，在尿毒症突触体中观察到ATP依赖性钙摄取显著增加（P < 0.005）。这些研究表明：（a）尿毒症大鼠脑制备的突触体中，通过Na+-Ca++交换器的钙积累增加。（b）与正常情况相比，尿毒症大鼠通过ATP依赖性钙转运机制进入倒置质膜囊泡的钙内流增加。（c）尿毒症中通过Na+-Ca++交换和ATP依赖性钙转运机制导致的钙积累增加似乎是突触体膜对钙通透性增加的结果。尿毒症中钙转运的这两种异常情况在体内均倾向于增加脑细胞外钙。在尿毒症中观察到的缺陷似乎不易逆转，且与PTH的关系目前尚不清楚。这些异常情况可能会影响尿毒症状态下的神经传递。
