DYNAMICS OF PH REGULATION IN BRAIN

大脑 PH 调节的动态

• 批准号: 6188143
• 负责人: MITCHELL CHESLER
• 金额: $ 20.44万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-09-01 至 2003-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6188143
• 关键词: acid base balance; astrocytes; bicarbonates; brain electrical activity; carbon dioxide; carbonate dehydratase; histochemistry /cytochemistry; intracellular transport; laboratory rat; microelectrodes; neurochemistry; neurons; neurophysiology; tissue /cell culture; voltage /patch clamp

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.

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变化很敏感 专注。 酸碱状态对大脑尤其重要 损伤，它可以在大脑的表现中发挥决定性作用 损伤和功能恢复。 正常的电活动也 导致间质和细胞内 pH 值发生巨大变化， 影响功能的速度和幅度。 这些 pH 值变化源自 神经元和神经胶质细胞的特殊机制，因此显示出明显的 区域异质性和刻板模式。 此举的目的 研究目的是确定控制 pH 动态行为的机制 中枢神经系统并阐明这些过程的作用 调节神经功能。 这一广泛目标将通过 研究两个条件下活性依赖性 pH 值变化的动态 细胞和区域级别。 碳酸酐酶的调节作用 间隙缓冲能力将是主要关注点。 这些 脑切片实验将利用新技术 pH 变化的时间分辨率在毫秒范围内。 结合这个 具有已建立的膜片钳方法的能力将允许分析 pH 值的变化直接调节兴奋性突触电流。 在水平上 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 解决钙流入和生成之间的关系 间质碱移。 星形胶质细胞的实验将集中于 这些细胞作为间质 pH 调节剂的作用。 调查情况 将受益于新型荧光和离子选择性的结合 微电极方法，能够解决 pH 值的实时变化， 碳酸氢盐和二氧化碳张力。 这些研究将提供 了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。