DYNAMICS OF PH REGULATION IN BRAIN

描述 PH值的调节对于大脑的正常运作至关重要，因为 许多通道和酶对氢离子的微小移动很敏感 集中精神。酸碱状态在大脑中可能特别重要 损伤，它可以在大脑的表现中起决定性作用 损伤和功能的恢复。正常的电活动也 导致细胞间质和细胞内pH的巨大变化， 影响功能的速度和大小。这些pH值的变化是由 神经元和神经胶质细胞的特殊机制，因此显示出明显的 区域异质性和刻板印象。这样做的目的是 研究目的是确定控制pH动态行为的机制 并阐明这些过程的作用 在调节神经功能方面。这一广泛的目标将通过以下方式实现 研究了活性依赖的pH变化在两个 蜂窝和区域层面。碳酸酐酶在调控中的作用 间隙缓冲能力将是主要关注的焦点。这些 在脑片上的实验将利用允许使用的新技术 PH值在毫秒范围内的时间分辨率。将这一点结合起来 已建立的膜片钳方法的能力将允许分析 直接调制兴奋性突触电流的PH值变化。在这个层面上 对于分离的细胞，注意力将转向特定的酸 神经元和星形胶质细胞的运输机制。神经元研究将 解决钙离子内流与血管生成的关系 间质碱性移位。对星形胶质细胞的实验将集中在 这些细胞作为间质pH调节器的作用。这项调查 将受益于新的荧光和离子选择性的组合 微电极方法，能够解决pH的实时变化， 小苏打和二氧化碳的张力。这些研究将提供一个 理解氢离子的功能作用，并增加对 中风和心脏骤停后pH调节的病理生理学。

DESCRIPTION The regulation of pH is critical for the normal operation of the brain, as numerous channels and enzymes are sensitive to small shifts in hydrogen ion concentration. Acid base status can be particularly important in brain injury, where it can play a determinant role in the manifestation of brain damage and the recovery of function. Normal electrical activity also results in large changes in interstitial and intracellular pH, of sufficient speed and magnitude to influence function. These pH shifts arise from specialized mechanisms in neurons and glia, and therefore display marked regional heterogeneity and stereotyped patterns. The objective of this study is to determine the mechanisms which govern the dynamic behavior of pH in the central nervous system and to elucidate the role of these processes in modulating neural function. This broad aim will be addressed by investigating the dynamics of activity-dependent pH shifts at both the cellular and regional level. The role of carbonic anhydrase in governing the interstitial buffering capacity will be a principal focus. These experiments on brain slices will utilize using new technologies that permit temporal resolution of pH shifts in the millisecond range. Combining this capability with established patch clamp methods will allow analysis of the pH change that directly modulate excitatory synaptic currents. At the level of the isolated cell, attention will be turned to the specific acid transport mechanisms of neurons and astrocytes. Neuronal studies will address the relationship between calcium influx and the generation of interstitial alkaline shifts. Experiments on astrocytes will focus on the role of these cells as regulators of interstitial pH. The investigation will benefit from the combination of novel fluorescence and ion-selective microelectrode methods, capable of resolving real time changes in pH, bicarbonate, and carbon dioxide tension. These studies will provide an understanding of the functional role of hydrogen ions and add insights into the pathophysiology of pH regulation following stroke and cardiac arrest.