Intracellular Acidification Causes Adenosine Release During States of Hyperexcitability in the Hippocampus
Intracellular Acidification Causes Adenosine Release During States of Hyperexcitability in the Hippocampus
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DOI：
10.1152/jn.90695.2008
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发表时间：
2009-09-01
影响因子：
2.5
通讯作者：
Masino, Susan A.
中科院分区：
文献类型：
--
作者：
Dulla, Chris G.;Frenguelli, Bruno G.;Masino, Susan A.
Dulla CG、Frenguelli BG、Staley KJ、Masino SA。在海马过度兴奋状态下，细胞内酸化会导致腺苷释放。 《神经生理学杂志》102：1984-1993，2009 年。首次发表于 2009 年 7 月 22 日； doi：10.1152/jn.90695.2008。 pH 值降低会增加中枢神经系统区域（如海马和腹髓质）的细胞外腺苷。然而，到目前为止，对于关键的 pH 变化是否是细胞内和/或细胞外 pH 值的降低还没有明确的共识。之前我们表明，为了增加急性海马切片制剂中的细胞外腺苷，降低细胞外 pH 值是必要的，仅降低细胞内 pH 值是不够的。在这里，我们进一步探讨了海马切片中不同突触条件下细胞内 pH 的作用。当突触兴奋性增加时，无论是在 CA1 中的 γ-氨基丁酸 A 型受体阻断期间，还是在 CA3 中诱导持续爆发后，仅降低细胞内 pH 就足以：1) 提高细胞外腺苷浓度，2) 激活腺苷 A 1 受体，3) 减少兴奋性突触传递 (CA1)，以及 4) 减弱体外癫痫模型中的爆发频率（CA3）。从腺苷 A 1 受体敲除小鼠获得的海马切片没有表现出这些 pH 介导的对突触传递的影响，进一步证实了腺苷作用于腺苷 A 1 受体的作用。总而言之，这些数据强化并显着增加了概述 pH 变化作为影响细胞外腺苷的重要刺激因素的证据。此外，我们还确定了细胞内 pH 在调节细胞外腺苷浓度中起主导作用的条件。
Dulla CG, Frenguelli BG, Staley KJ, Masino SA. Intracellular acidification causes adenosine release during states of hyperexcitability in the hippocampus. J Neurophysiol 102: 1984-1993, 2009. First published July 22, 2009; doi:10.1152/jn.90695.2008. Decreased pH increases extracellular adenosine in CNS regions as diverse as hippocampus and ventral medulla. However, thus far there is no clear consensus whether the critical pH change is a decrease in intracellular and/or extracellular pH. Previously we showed that a decrease in extracellular pH is necessary and a decrease in intracellular pH alone is not sufficient, to increase extracellular adenosine in an acute hippocampal slice preparation. Here we explored further the role of intracellular pH under different synaptic conditions in the hippocampal slice. When synaptic excitability was increased, either during gamma-aminobutyric acid type A receptor blockade in CA1 or after the induction of persistent bursting in CA3, a decrease in intracellular pH alone was now sufficient to: 1) elevate extracellular adenosine concentration, 2) activate adenosine A 1 receptors, 3) decrease excitatory synaptic transmission (CA1), and 4) attenuate burst frequency in an in vitro seizure model (CA3). Hippocampal slices obtained from adenosine A 1 receptor knockout mice did not exhibit these pH-mediated effects on synaptic transmission, further confirming the role of adenosine acting at the adenosine A 1 receptor. Taken together, these data strengthen and add significantly to the evidence outlining a change in pH as an important stimulus influencing extracellular adenosine. In addition, we identify conditions under which intracellular pH plays a dominant role in regulating extracellular adenosine concentrations.