Zhang E T, Hansen A J, Wieloch T, Lauritzen M
Department of General Physiology and Biophysics, University of Copenhagen, Denmark.
J Cereb Blood Flow Metab. 1990 Jan;10(1):136-9. doi: 10.1038/jcbfm.1990.18.
The purpose of the present study was to examine the effect of blockade of N-methyl-D-aspartate (NMDA) receptors on the depolarization associated with severe hypoglycemia, which is commonly preceded by one or a few transient depolarizations reminiscent of cortical spreading depression (CSD). In the cerebral cortices of rats [K+]e and [Ca2+]e were measured with ion-selective microelectrodes. NMDA blockade was achieved by injection of MK801 in doses that block CSD. In control rats, the latency from the time point when blood glucose reached minimal levels to onset of ionic shifts was 33.2 +/- 3.5 min, and [K+]e rose from 3.2 +/- 0.2 to 55 +/- 5 mM. All variables remained unchanged in rats treated with MK801. In another four rats treated with MK801, [Ca2+]e declined from 1.06 +/- 0.22 to 0.12 +/- 0.02 mM. Plasma glucose measurements indicated that the cortex depolarized at a plasma glucose concentration between 0.7 and 0.8 mM, i.e., within a narrow range, suggesting a threshold phenomenon. In conclusion, activation of NMDA receptors seems of minor importance for hypoglycemic depolarization. The ionic transients that precede the persistent hypoglycemic depolarization are probably mediated by mechanisms distinct from those of electrically induced CSD.
本研究的目的是检测N-甲基-D-天冬氨酸（NMDA）受体阻断对与严重低血糖相关的去极化的影响，严重低血糖通常先出现一个或几个短暂的去极化，类似于皮层扩散性抑制（CSD）。在大鼠大脑皮层中，用离子选择性微电极测量细胞外钾离子浓度（[K+]e）和细胞外钙离子浓度（[Ca2+]e）。通过注射能阻断CSD的剂量的MK801来实现NMDA受体阻断。在对照大鼠中，从血糖达到最低水平的时间点到离子变化开始的潜伏期为33.2±3.5分钟，[K+]e从3.2±0.2毫摩尔/升升至55±5毫摩尔/升。用MK801处理的大鼠所有变量均保持不变。在用MK801处理的另外四只大鼠中，[Ca2+]e从1.06±0.22毫摩尔/升降至0.12±0.02毫摩尔/升。血浆葡萄糖测量表明，皮层在血浆葡萄糖浓度为0.7至0.8毫摩尔/升之间去极化，即在一个狭窄范围内，提示存在阈值现象。总之，NMDA受体的激活对低血糖去极化似乎不太重要。持续性低血糖去极化之前的离子瞬变可能由不同于电诱导CSD的机制介导。
