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.

Elevated brain lactate responses to neural activation in panic disorder: a dynamic 1H-MRS study

“…6,8 Neuronal activity is often followed by intracellular alkalinization within astrocytes and acidification of brain ECF. 64 The degree of activity-evoked ECF acidification has been correlated with lactate accumulation. 65 Episodes of exaggerated activity-evoked lactate accumulation in chemosensitive nuclei could be integral to the process that triggers the unwarranted arousal reactions, as well as respiratory and autonomic changes, characteristic of spontaneous panic attacks.…”

Supportive or information-processing functions of the mature protoplasmic astrocyte in the mammalian CNS? A critical appraisal

“…The current assumption seems to be that an effect of altering fusion proteins in astrocytes on neuron-based electrophysiological activities does indicates modulation of synaptic activity in an initiating manner, but this does not seem to follow. If it did then, logically, the same reasoning would apply to changes in, for example, H + -transporting systems such as Cl − /HCO 3 − and Na + /H + exchangers that are involved in maintaining [H + ] o in the face of changes caused by neuronal activity (Newman, 1999;Chesler, 2003 The key point from the studies referred to above is that, when a transmitter is released from astrocytic processes by Ca 2+ -dependent fusion of vesicles that store the transmitter, it indicates crucial control of synaptic events that is equivalent to the control of information flow. However, we then add to the unknown complexity of neuronal information-processing a need to understand what controls the astrocyte control, and so on.…”

“…Several either electrically neutral or electrogenic K + or H + transporters were identified originally in primary astrocyte cultures (Kimelberg et al, 1979) and then in astrocytes in situ (Deitmer and Schneider, 2000;Chesler, 2003). However, these transporters are essentially ubiquitous, so this is not definitive for astrocytes.…”

“…However, these transporters are essentially ubiquitous, so this is not definitive for astrocytes. It was hypothesized that they would also buffer K + (such as the Na+K+2Cl co-transporter) and H + (via Na/H and HCO 3 transporting systems) (Kimelberg et al, 1979;Chesler, 2003). Uptake by either transporters or coupled cation plus anion uptake on separate channels might then be followed by diffusion and dilution within the syncytium.…”

ASIC3 Channels in Multimodal Sensory Perception

“…Generally, the acidic pH can be categorized as mild and extreme acidosis, although there is no absolute cutoff point. Mild acidosis (pH 7.0, Figure 2, panel a) induces both a transient current and a sustained window current (39), while extreme acidosis For example, the rapidly desensitizing ASIC3 current argues that ASIC3 is best suited to respond to rapid pH fluctuations under certain physiological conditions (44). It is reasonable to hypothesize that touch stimuli activate ASIC3 channels through the rapid release of protons, generating a rapidly adapting response in the touch receptor.…”