PH REGULATION AND PROTON SIGNALING BY GLIAL-CELLS

The regulation of H+ in nervous systems is a function of several proce sses, including H+ buffering, intracellular H+ sequestering, CO2 diffu sion, Carbonic anhydrase activity and membrane transport of acid/base equivalents across the cell membrane. Glial cells participate in all t hese processes and therefore play a prominent role in shaping acid/bas e shifts in nervous systems. Apart from B homeostatic function of H+-r egulating 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 hormone s as well as secondary to metabolic activity and ionic membrane transp ort. A pivotal role for H+ regulation and shaping these pH transients must be assigned to the electrogenic and reversible Na+ - HCO3- membra ne cotransport, which appears to be unique to glial cells in nervous s ystems. Activation of this cotransporter results in the release and up take of base equivalents by glial cells, processes which are dependent on the glial membrane potential. Na+/H+ and Cl-/HCO3- exchange, and p ossibly other membrane carriers, accomplish the set of tools in both g lial 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 communic ation 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 dis cussed for a variety of nervous system functions.