pH regulation and proton signalling by glial cells.

The regulation of H+ in nervous systems is a function of several processes, including H+ buffering, intracellular H+ sequestering, CO2 diffusion, carbonic anhydrase activity and membrane transport of acid/base equivalents across the cell membrane. Glial cells participate in all these processes and therefore play a prominent role in shaping acid/base shifts in nervous systems. Apart from a homeostatic function of H(+)-regulating mechanisms, pH transients occur in all three compartments of nervous tissue, neurones, glial cells and extracellular spaces (ECS), in response to neuronal stimulation, to neurotransmitters and hormones as well as secondary to metabolic activity and ionic membrane transport. A pivotal role for H+ regulation and shaping these pH transients must be assigned to the electrogenic and reversible Na(+)-HCO3-membrane cotransport, which appears to be unique to glial cells in nervous systems. Activation of this cotransporter results in the release and uptake of base equivalents by glial cells, processes which are dependent on the glial membrane potential. Na+/H+ and Cl-/HCO3-exchange, and possibly other membrane carriers, accomplish the set of tools in both glial cells and neurones to regulate their intracellular pH. Due to the pH dependence of a great variety of processes, including ion channel gating and conductances, synaptic transmission, intercellular communication via gap junctions, metabolite exchange and neuronal excitability, rapid and local pH transients may have signalling character for the information processing in nervous tissue. The impact of H+ signalling under both physiological and pathophysiological conditions will be discussed for a variety of nervous system functions.