Mutch W A, Hansen A J
J Cereb Blood Flow Metab. 1984 Mar;4(1):17-27. doi: 10.1038/jcbfm.1984.3.
We have examined the extracellular pH (pHe) during spreading depression and complete cerebral ischemia in rat parietal cortex utilizing double-barrelled H+ liquid ion exchanger microelectrodes. The baseline pHe of the parietal cortex was 7.33 at a mean arterial PCO2 of 38 mm Hg. Following spreading depression and cerebral ischemia, highly reproducible triphasic changes in pHe occurred, which were intimately related to the negative deflection in tissue potential (Ve). The changes in pHe for spreading depression (n = 23) were a small initial acidic shift, beginning before the rapid change in Ve, followed by a rapid transient alkaline shift of 0.16 pH units, the onset of which coincided with the negative deflection in Ve. A prolonged acidic shift of 0.42 pH units then occurred. The maximal decrease in pHe was to 6.97 and the mean duration of the triphasic pHe change was 7.8 min. The lactate concentration in brain cortex increased from baseline 1.2 mM to 7.0 mM (n = 6) during the maximal acidic change in spreading depression. In addition, lactate levels correlated well with resolution of the pHe changes during spreading depression. The triphasic pHe changes following complete cerebral ischemia were an initial acidic shift of 0.43 pH units which developed over 2 min, then an alkaline shift of 0.10 pH units coincident with the negative deflection in Ve, and a final acidic shift of 0.26 pH units. The terminal pHe was 6.75. Superfusion of the cortex with inhibitors of carbonic anhydrase (acetazolamide), Na+/H+ counter transport (amiloride), and Cl-/HCO-3 countertransport (4,4'-diisothiocyanostilbene-2,2'-disulfonic acid) altered the triphasic pHe changes in a similar fashion for both spreading depression and cerebral ischemia, providing insights into the pHe regulatory mechanisms in mammalian brain.
我们利用双管H⁺液体离子交换微电极，检测了大鼠顶叶皮质在扩散性抑制和完全性脑缺血过程中的细胞外pH值（pHe）。在平均动脉血二氧化碳分压为38 mmHg时，顶叶皮质的基线pHe为7.33。在扩散性抑制和脑缺血后，pHe出现了高度可重复的三相变化，这与组织电位（Ve）的负向偏转密切相关。扩散性抑制（n = 23）时pHe的变化是：最初有一个小的酸性偏移，在Ve快速变化之前开始，随后是0.16个pH单位的快速短暂碱性偏移，其起始与Ve的负向偏转同时发生。然后出现了0.42个pH单位的长时间酸性偏移。pHe的最大下降值为6.97，三相pHe变化的平均持续时间为7.8分钟。在扩散性抑制的最大酸性变化期间，脑皮质中的乳酸浓度从基线的1.2 mM增加到7.0 mM（n = 6）。此外，乳酸水平与扩散性抑制期间pHe变化的恢复密切相关。完全性脑缺血后的三相pHe变化是：最初在2分钟内出现0.43个pH单位的酸性偏移，然后是与Ve负向偏转同时发生的0.10个pH单位的碱性偏移，以及最后的0.26个pH单位的酸性偏移。最终的pHe为6.75。用碳酸酐酶抑制剂（乙酰唑胺）、Na⁺/H⁺逆向转运抑制剂（氨氯地平）和Cl⁻/HCO₃⁻逆向转运抑制剂（4,4'-二异硫氰酸芪-2,2'-二磺酸）对皮质进行灌流，对扩散性抑制和脑缺血的三相pHe变化产生了类似的改变，这为了解哺乳动物脑内pHe调节机制提供了线索。
