ALKALINE AND ACID TRANSIENTS IN CEREBELLAR MICROENVIRONMENT
ALKALINE AND ACID TRANSIENTS IN CEREBELLAR MICROENVIRONMENT
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DOI：
10.1152/jn.1983.49.3.831
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发表时间：
1983-01-01
影响因子：
2.5
通讯作者：
NICHOLSON, C
中科院分区：
文献类型：
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作者：
KRAIG, RP;FERREIRAFILHO, CR;NICHOLSON, C
用新近研制的液膜离子选择性微量移液器（ISM）测定了大鼠小脑皮质细胞外pH值（pHo）。在刺激诱发的神经元活动、升高的细胞外K浓度、[K+]o、扩散性抑制（SD）和完全缺血期间测定pH。在许多实验中，同时测定[K+]o。一系列的局部表面刺激（ESTA）产生的初始碱性偏移的pH值从基线的7.20-7.30到7.25-7.35。随后是一个持久的酸相，在刺激64秒后达到7.05-7.15的平台。pHo降低与刺激频率、强度和持续时间有关。灌流含有Mn ~（2+）的林格氏液迅速消除了平行纤维诱导的浦肯野细胞突触去极化以及碱性移位，同时增强了酸性移位。用含有逐渐升高的[K+]的林格溶液灌注小脑皮质，使pH值逐渐降低至6.95-7.05的平台。在哇巴因的存在下发生酸化，但在恢复正常[K+]o或加入糖酵解阻滞剂氟化物后发生逆转。刺激诱发的碱性移位增强K+-林格灌流。酸转移可能是由于代谢产生的阴离子，可能是乳酸盐。当[K+]o升高到8-12 mM时，pH和[K+]o的振荡周期约为40 s。有时这些振荡以自发SD结束，或SD可由刺激诱发。在[K+]o升高的这些条件下，SD由非常明显的碱性瞬变以及随后的小的、持久的酸转变组成。当SD诱导小脑条件丙酸盐或降低NaCl，碱性相减少，酸性增强。完全缺血开始时pHo逐渐降低，[K+]o逐渐升高。当[K+]o达到12 mM时，[K+]o第二次更快速地上升至≥出现40 mM。这与0.1-0.2 pHo一过性升高相关，与SD期间观察到的相似。pH最终达到6.60-6.80的平台，接近中性。灌流林格氏溶液含有乙酰唑胺立即改变pH值的稳态增加基线pH值约0.10，并增强诱导的pH值的变化。显然，碳酸酐酶（CA）是重要的急性缓冲脑细胞外微环境。这些结果被解释为细胞外强离子浓度差（[SID]o），细胞外总弱酸浓度（[Atot]o）和脑微环境中CO2分压（PCO 2）的变化。神经元活动可能引起微环境中许多成分的变化。
Extracellular pH (pHo) was measured in the cerebellar cortex of the rat using a recently developed liquid membrane ion-selective micropipette (ISM). pHo was determined during stimulus-evoked neuronal activity, elevated extracellular K concentration, [K+]o, spreading depression (SD), and complete ischemia. In many experiments [K+]o was simultaneously determined. A train of local surface stimuli (LOC) produced an initial alkaline shift in pHo from a base line of 7.20-7.30 to 7.25-7.35. This was followed by a long-lasting acid phase that reached a plateau of 7.05-7.15 after 64 s of stimulation. pHo decrease was related to stimulus frequency, intensity and duration. Superfusion with Ringer solution containing Mn2+ rapidly abolished parallel fiber-induced Purkinje cell synaptic depolarization together with the alkaline shifts while enhancing the acid shifts. Superfusion of the cerebellar cortex with Ringer solution containing increasingly elevated [K+] progressively lowered pHo to a plateau of 6.95-7.05. The acidification occurred in the presence of ouabain but was reversed on return to the normal [K+]o or with the addition of the glycolytic blocker, fluoride. Stimulus-evoked alkaline shifts were enhanced by K+-Ringer superfusion. The acid shift was probably due to the metabolic production of an anion, possibly lactate. Elevation of [K+]o above 8-12 mM often produced oscillation in pHo and [K+]o with a period of about 40 s. Sometimes these oscillations ended in a spontaneous SD or SD could be evoked by stimulation. Under these conditions of raised [K+]o, the SD consisted of a very pronounced alkaline transient followed by a small, long-lasting acid shift. When SD was induced by conditioning the cerebellum with propionate or lowered NaCl, the alkaline phase was reduced and the acid enhanced. Complete ischemia began with a progressive decrease of pHo and rise in [K+]o. When [K+]o reach 12 mM, a 2nd more rapid rise in [K+]o to .gtoreq. 40 mM occurred. This was correlated with 0.1-0.2 pHo transient increase similar to that seen during SD. pHo eventually reached a plateau of 6.60-6.80, close to neutrality. Superfusion with Ringer solution containing acetazolamide immediately altered pHo homeostasis by increasing base-line pHo by about 0.10 and enhanced the induced pHo changes. Apparently, carbonic anhydrase (CA) is important for acute buffering of the brain extracellular microenvironment. These results were interpreted in terms of changes in extracellular strong ion concentration differences ([SID]o), extracellular concentration of total weak acid ([Atot]o) and partial pressure of CO2 (PCO2) in the brain microenvironment. Neuronal activity probably produces changes in many of the constituents of the microenvironment.