Invited Symposium: Na-H Exchangers and Intracellular pH Regulation PH SIGNALLING INDUCED BY NEURONAL ACTIV PH SHIFTS IN THE NEURON-GLIA DIALOGUE |
Abstract Glial cells provide an essential contribution to pH regulation and acid/base transients in nervous systems. The mechanisms of intracellular pH regulation and the transport of neurotransmitters and metabolites across the glial cell membrane also shape extracellular pH shifts. These pH transients can be very brief and local, and may constitute a proton-mediated signalling between glial cells and neurons (Deitmer & Rose, 1996). The largest, and probably most significant pHi changes appear to be contributed by the neurotransmitters, by Na+/H+ exchange and by the reversible, electrogenic Na+-HCO3- cotransporter as well as by organic acid transporters and metabolic processes. With respect to the action of neurotransmitters on pHi and most pHi-regulating mechanisms, glial cells appear to resemble neurons, while the electrogenic Na+-HCO3- cotransporter, reminiscent of epithelial cells, exists exclusively in glial cells in nervous systems. For nearly all events related to pH changes in nervous tissue, the presence of CO2 and HCO3- has a great impact. HCO3- determines the buffering power to a large extent, it enables HCO3- flux through GABAA and glycine receptor channels, and thereby modifies the inhibitory synaptic potentials, and it stimulates the powerful glial electrogenic Na+-HCO3- cotransporter and other carriers such as Na+-dependent and Na+-independent Cl-/HCO3- exchange. CO2, as an inert gas, which easily permeates membranes, rapidly dissipates from any location where it is formed through cells and tissues, and together with a high enzyme activity of carbonic anhydrase provides an effective and high buffer capacity even at relatively low concentrations. Considering H+ transients as signals, CO2, HCO3- and carbonic anhydrase are essential elements in this signalling, determining the shape of the pH shifts in time and space within nervous systems. Deitmer, J.W. & Rose, C.R. (1996). Progr. Neurobiol. 48, 73-103. Supported by the Deutsche Forschungsgemeinschaft
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Deitmer, JW; (1998). Proton Signalling and pH Regulation in Glial Cells. Presented at INABIS '98 - 5th Internet World Congress on Biomedical Sciences at McMaster University, Canada, Dec 7-16th. Invited Symposium. Available at URL http://www.mcmaster.ca/inabis98/fliegel/deitmer0365/index.html | ||||||||
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