VDM Tong, C: The role of pH in Brain Function

The pH of a tissue is important to influence biological processes. Although there are mechanisms to maintain pH in the brain, there occur endogenous extracellular pH changes in brain tissue either in a normal context, such as electrical stimuli, or in a pathological context, such as spreading depression (SD). Because the pH changes can spread to influence biological function at a distance, it can be regarded as a putative signal. CO2-HCO3- is the major buffering system in the extracellular space and extracellular carbonic anhydrase (ECA) is important for modulating the pH signals. We discovered that membrane-bound CA type IV, not soluble form type II, is the major ECA to modulate the extracellular buffering capacity. We further identified that ECA can modulate the amplitude of the endogenous alkalosis during SD and influence NMDA receptor function. Upon studying the time course of the activity-dependent alkalosis, ECA was found ineffective to buffer the stimulus-dependent alkaline shift within fast time frame. These results suggest that CA IV, although present in a low concentration, has an important modulatory effect on the extracellular pH transients in brain tissue.