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Control and modulation of intracellular pH in mammalian central neurones

Amos, Brian John; (1995) Control and modulation of intracellular pH in mammalian central neurones. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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This thesis describes single cell microfluorimetry studies of intracellular pH (pHi) in rat central neurones maintained in culture. The work aimed to determine the proton buffering power of these neurones as well as define the contribution of CO2 to this buffering. Furthermore, the relationship between buffering power and pH was to be investigated as well as the nature of pHi-regulating transport mechanisms present in these cells. In addition to investigating these pHi homeostatic mechanisms, the modulation of neuronal pHi by neurotransmitter action was investigated. In order to estimate proton buffering power, cells were challenged with a variety of weak acids and bases (NH4CI, trimethylamine, butyric acid, CO2). Experiments performed in the absence of CO2/HCO3- yielded estimates of intrinsic buffering power (10mmoles/1 at pH 7.25). In the presence of CO2 buffer, estimates of total buffering power were obtained. The contribution of CO2 to proton buffering appeared to be minimal. Furthermore, the presence of a carbonic anhydrase inhibitor had no effect on estimates of total buffering power. The values of buffering power appeared to be independent of the acid/base used to obtain them, with the exception of those estimated using butyric acid. In this latter case some monocarboxylate ion transport apparently occured causing an overestimation of buffering power. Both total and intrinsic proton buffering were found to increase with decreasing pH over the range measured (6.7-7.7). The method of measuring buffering power was such that pHi-regulating mechanisms had a negligible effect on buffering power estimates. The effect of glutamatergic agonists on neuronal pHi were investigated. Challenges of 50[mu]M L-glutamate, or the metabotropic glutamate agonist tACPD, elicited a sustained intracellular acidification. In HEPES buffer these acidifications took the form of a step change in pHi whereas in CO2 buffer a continuous decline in pHi was observed. One mechanism by which the metabotropic glutamate receptor agonist appeared to work was via suppression of a bicarbonate-dependent pHi-regulating process. This effect was possibly G-protein mediated.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Control and modulation of intracellular pH in mammalian central neurones
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Biological sciences
URI: https://discovery.ucl.ac.uk/id/eprint/10103277
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