Schlue W R, Deitmer J W
Institut für Zoologie, Lehrstuhl für Neurobiologie, Universität Düsseldorf, Federal Republic of Germany.
Ciba Found Symp. 1988;139:47-69. doi: 10.1002/9780470513699.ch4.
Two separate mechanisms responsible for intracellular pH (pHi) regulation in neuronal membranes of the nervous system have been studied so far: they are Na+/H+ and Na+-H+-HCO3-/Cl- exchange. The involvement of these mechanisms in pHi regulation of neurons and glial cells has been investigated in the leech central nervous system using ion-selective microelectrodes. The amiloride-sensitive Na+/H+ exchange is the predominant mechanism of pHi regulation in nominally HCO3- free, Hepes-buffered saline of both neurons and glial cells of this nervous system. In the presence of CO2-HCO3- buffer, however, the SITS-sensitive Na+-H+-HCO3-/Cl- exchanger contributes to acid extrusion in neurons and probably also in glial cells. Unlike neuronal pHi, glial pHi increases when Hepes is replaced by CO2-HCO3- as the extracellular buffer, and decreases again on return to Hepes buffer. The glial alkalinization occurs in the opposite direction, as would be expected from the CO2 movement across the cell membrane and its hydration to form carbonic acid which dissociates into H+ and HCO3- ions. The expected acidification, however, is observed in neurons, and is reduced by acetazolamide and ethoxzolamide, inhibitors of carbonic anhydrase, which catalyses the formation of carbonic acid. On the other hand, these drugs are shown to produce no change of the CO2-HCO3- -induced alkalinization in glial cells. The observations suggest that Na+-HCO3- co-transport across the glial cell membrane, mediating the influx of HCO3- ions into the cell interior, could be responsible for the unusual alkalinization. Further evidence for the activation of Na+-HCO3- co-transport, as a third mechanism involved in pHi homeostasis of the nervous system, is presented.
迄今为止，已经对神经系统神经元膜中负责细胞内pH值（pHi）调节的两种独立机制进行了研究：它们是Na⁺/H⁺交换和Na⁺-H⁺-HCO₃⁻/Cl⁻交换。利用离子选择性微电极在水蛭中枢神经系统中研究了这些机制在神经元和神经胶质细胞pHi调节中的作用。在该神经系统的神经元和神经胶质细胞的名义上无HCO₃⁻的Hepes缓冲盐溶液中，氨氯地平敏感的Na⁺/H⁺交换是pHi调节的主要机制。然而，在存在CO₂-HCO₃⁻缓冲液的情况下，SITS敏感的Na⁺-H⁺-HCO₃⁻/Cl⁻交换体有助于神经元以及可能也有助于神经胶质细胞排出酸。与神经元pHi不同，当用CO₂-HCO₃⁻替代Hepes作为细胞外缓冲液时，神经胶质细胞pHi会升高，而回到Hepes缓冲液时又会再次降低。神经胶质细胞碱化的方向与之相反，这与CO₂穿过细胞膜及其水合形成碳酸并解离成H⁺和HCO₃⁻离子的预期情况相符。然而，在神经元中观察到了预期的酸化，并且被碳酸酐酶抑制剂乙酰唑胺和乙氧唑胺所减弱，碳酸酐酶催化碳酸的形成。另一方面，这些药物在神经胶质细胞中并未显示出对CO₂-HCO₃⁻诱导的碱化有任何影响。这些观察结果表明，Na⁺-HCO₃⁻协同转运穿过神经胶质细胞膜，介导HCO₃⁻离子流入细胞内部，可能是这种异常碱化的原因。本文还提供了进一步的证据，证明Na⁺-HCO₃⁻协同转运的激活是参与神经系统pHi稳态的第三种机制。
