Ventrolateral neurons of medullary organotypic cultures: intracellular pH regulation and bioelectric activity

Martin Wiemann, Dieter Bingmann
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引用次数: 42

Abstract

The hypothesized role of the intracellular pH (pHi) as a proximate stimulus for central chemosensitive neurons is reviewed on the basis of data obtained from organotypic cultures of the medulla oblongata (obex level) of new born rats (OMC). Within OMC a subset of neurons responds to hypercapnia as do neurons in the same (or similar) brain areas in vivo. Maneuvers altering intra- and/or extracellular pH (pHo) such as hypercapnia, bicarbonate-withdrawal, or ammonium pre-pulses, evoked well defined changes of the neuronal pHi. During hypercapnia (pHo 7.0) or bicarbonate-withdrawal (pHo 7.4) most ventrolateral neurons adopted a pHi which was ≤0.2 pH units below the steady state pHi, while signs of pHi-regulation occurred only in a small fraction of neurons. During all treatments leading to intracellular acidosis, bioelectric activity of chemosensitive neurons increased and was often indistinguishable from the response to hypercapnia, regardless of whether pHo was unchanged, decreased or increased during the treatment. These data strongly suggest that the pHi acts as proximate stimulus. The mode of acid extrusion of chemosensitive neurons is, therefore, of major importance for the control of central chemosensitivity. Immunocytochemical data, pHi measurements and neuropharmacological studies with novel drugs pointed to the Na+/H+ exchanger subtype 3 (NHE3) as a main acid extruder in ventrolateral chemosensitive neurons. Possible functions and neuropharmacological strategies arising from this very local NHE3 expression are discussed.

髓质器官型培养的腹外侧神经元:细胞内pH调节和生物电活性
基于新生大鼠延髓(obx水平)的器官型培养数据,对细胞内pH (pHi)作为中枢化学敏感神经元的近似刺激的假设作用进行了综述。在OMC中,一个神经元子集对高碳酸血症做出反应,就像体内相同(或相似)脑区域的神经元一样。改变细胞内和/或细胞外pH值(pHo)的操作,如高碳酸血症、碳酸氢盐戒断或铵预脉冲,可引起神经元pHi的明确变化。在高碳酸盐(pHo 7.0)或碳酸氢盐戒断(pHo 7.4)时,大多数腹侧神经元的pHi值低于稳态pHi值≤0.2个pH单位,而只有一小部分神经元出现了pHi调节的迹象。在所有导致细胞内酸中毒的治疗过程中,化学敏感神经元的生物电活性增加,并且通常与高碳酸血症的反应难以区分,无论在治疗期间pHo是不变,降低还是增加。这些数据有力地表明pHi起着近似刺激的作用。因此,化学敏感神经元的酸挤压模式对中枢化学敏感性的控制具有重要意义。免疫细胞化学数据、pHi测量和新型药物的神经药理学研究表明,Na+/H+交换器亚型3 (NHE3)是腹侧化学敏感神经元的主要酸挤出剂。可能的功能和神经药理学策略引起的这种非常局部的NHE3表达进行了讨论。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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