Regulation and Modulation of pH in the Brain

Abstract

The regulation of pH is a vital homeostatic function shared by all tissues. Mechanisms that govern H+ in the intracellular and extracellular fluid are especially important in the brain, because electrical activity can elicit rapid pH changes in both compartments. These acid-base transients may in turn influence neural activity by affecting a variety of ion channels. The mechanisms responsible for the regulation of intracellular pH in brain are similar to those of other tissues and are comprised principally of forms of Na+/H+ exchange, Na+-driven Cl-/HCO3- exchange, Na+-HCO3- cotransport, and passive Cl-/HCO3- exchange. Differences in the expression or efficacy of these mechanisms have been noted among the functionally and morphologically diverse neurons and glial cells that have been studied. Molecular identification of transporter isoforms has revealed heterogeneity among brain regions and cell types. Neural activity gives rise to an assortment of extracellular and intracellular pH shifts that originate from a variety of mechanisms. Intracellular pH shifts in neurons and glia have been linked to Ca2+ transport, activation of acid extrusion systems, and the accumulation of metabolic products. Extracellular pH shifts can occur within milliseconds of neural activity, arise from an assortment of mechanisms, and are governed by the activity of extracellular carbonic anhydrase. The functional significance of these compartmental, activity-dependent pH shifts is discussed.

Acute neuroinflammation provokes intracellular acidification in mouse hippocampus

“…In our experiments, control pHi and pHo levels were about 7.1 and 7.3, respectively. These values are consistent with the measurements observed in other studies [3, 16, 47, 48] indicating that the slices were in good health in our experimental conditions. Acute neuroinflammation, induced by either i.p.…”

Acute neuroinflammation provokes intracellular acidification in mouse hippocampus

“…In our experiments, control pHi and pHo levels were about 7.1 and 7.3, respectively. These values are consistent with the measurements observed in other studies [3, 16, 47, 48] indicating that the slices were in good health in our experimental conditions. Acute neuroinflammation, induced by either i.p.…”

Rescue of hyperexcitability in hippocampal CA1 neurons from Mecp2 (-/y) mouse through surface potential neutralization

“…One unit shifts in the pH (6.4 and 8.4) from a normal pH of 7.4 were selected to impose clearly observable effects. These values are similar to the pH variations measured in the brain [ 12 ].…”

Genetically encoded proton sensors reveal activity-dependent pH changes in neurons

“…Consistent with previous work, we found that the time of maximum acidity correlated with seizure termination (Xiong et al, 2000). This is consistent with the idea that activity-dependent intracellular acidification may serve as a local feedback signal that dampens network excitability (Chesler, 2003). We were also able to detect differences in the temporal properties of pH shifts induced by the two separate seizure models.…”

Acute neuroinflammation provokes intracellular acidification in mouse hippocampus

“…In our experiments, control pHi and pHo levels were about 7.1 and 7.3, respectively. These values are consistent with the measurements observed in other studies [3, 16, 47, 48] indicating that the slices were in good health in our experimental conditions. Acute neuroinflammation, induced by either i.p.…”

Rescue of hyperexcitability in hippocampal CA1 neurons from Mecp2 (-/y) mouse through surface potential neutralization

“…One unit shifts in the pH (6.4 and 8.4) from a normal pH of 7.4 were selected to impose clearly observable effects. These values are similar to the pH variations measured in the brain [ 12 ].…”

Genetically encoded proton sensors reveal activity-dependent pH changes in neurons

“…Consistent with previous work, we found that the time of maximum acidity correlated with seizure termination (Xiong et al, 2000). This is consistent with the idea that activity-dependent intracellular acidification may serve as a local feedback signal that dampens network excitability (Chesler, 2003). We were also able to detect differences in the temporal properties of pH shifts induced by the two separate seizure models.…”

Acute neuroinflammation provokes intracellular acidification in mouse hippocampus

“…In our experiments, control pHi and pHo levels were about 7.1 and 7.3, respectively. These values are consistent with the measurements observed in other studies [3, 16, 47, 48] indicating that the slices were in good health in our experimental conditions. Acute neuroinflammation, induced by either i.p.…”

Rescue of hyperexcitability in hippocampal CA1 neurons from Mecp2 (-/y) mouse through surface potential neutralization

“…One unit shifts in the pH (6.4 and 8.4) from a normal pH of 7.4 were selected to impose clearly observable effects. These values are similar to the pH variations measured in the brain [ 12 ].…”

Genetically encoded proton sensors reveal activity-dependent pH changes in neurons

“…Consistent with previous work, we found that the time of maximum acidity correlated with seizure termination (Xiong et al, 2000). This is consistent with the idea that activity-dependent intracellular acidification may serve as a local feedback signal that dampens network excitability (Chesler, 2003). We were also able to detect differences in the temporal properties of pH shifts induced by the two separate seizure models.…”