published_or_final_version / Medicine / Doctoral / Doctor of Philosophy

The catalytic effect of potassium on the rate of CO₂ gasification of a bituminous coal char and a pure carbon substrate is investigated. The gasification rate depends on both the catalyst concentration (K/C atomic ratio) and the internal porous structure of the solid. For low values of the K/C atomic ratio, the initial gasification rate (mg carbon gasified per initial gram carbon per min) increases sharply with the addition of catalyst; at higher values, the rate profile levels off. The sharp increase in rate is due to the activation of reaction sites while the plateau is attributed to the saturation of the surface with active sites. The variation of the instantaneous gasification rate (based on remaining carbon) with carbon conversion at various initial K/C ratios is studied. The important reasons for the change in rate are the change in the solid surface area, the loss of active sites, the loss of catalyst by vaporization and the change in the K/C ratio due to carbon depletion. The loss of catalyst from the pure carbon substrate by vaporization is also determined. The extent of this loss depends primarily on the reaction start-up procedure. Temperature programmed experiments show that under inert atmospheres, both KOH and K₂CO₃ react with carbon to give a reduced form of the catalyst which appears to be a prerequisite for the rapid vaporization of potassium. The effect of catalyst loss on both the initial gasification rate and the variation in rate with conversion is determined. The reaction mechanism is studied by a temperature and concentration programmed reaction technique. The proposed redox mechanism contains three surface complexes: -CO₂K, -COK and -CK. The oxide groups are the intermediates during C/CO₂ gasification. The completely reduced form, -CK, is the end product of catalyst reduction and is the precursor for K loss. The stoichiometries of these surface groups are confirmed by oxygen and potassium balance.

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Members of the two-pore potassium-selective (K2P) ion channel superfamily control cell excitability by contributing to the resting membrane potential. Through this, K2P channels are involved in a variety of physiological processes and dysfunction of these channels has been linked to diseases such as epilepsy, depression and migraine. The aim of this study was to develop a greater understanding of how K2P channels, in particular TREK-1, are gated. In the initial stage of this study we hoped to identify mutations which alter the function of the TREK-1 channel by screening a random mutant library using a K+-auxotrophic strain of S. cerevisiae, SGY1528. From the assay we identified a number of gain-of-function (GoF) mutations, primarily distributed through the pore-lining transmembrane (TM) helices TM2 and TM4. The clustering of mutations in these regions suggested a major role for these helices in channel gating. Subsequent electrophysiological characterisation of these mutations revealed an increase in basal channel activity and altered sensitivity to modulation by extracellular pH, as well as by activators DEPC and BL-1249. The publication of two K2P channel crystal structures, TWIK-1 (pdb code: 3UKM) and TRAAK (3UM7), enabled us to build an accurate homology model of TREK-1 and more accurately interpret these functional studies. This approach revealed a number of interesting points, the most important being an interaction between TM4 and pore-helix 1 (PH1). Further mutagenesis studies of this region confirmed that this interaction is essential for normal channel function. Another interaction was identified involving a number of residues within the interface between TM helices TM2, TM3 and TM4 emphasised the importance of helical movements for gating TREK-1 channels. Based on our findings we therefore present a model for gating of the TREK-1 channel, which suggests that the movement of TM4 in particular, is transduced to the selectivity filter gate via PH1.

The purpose of this study, therefore, was threefold in nature: (1) to determine the effects of x-irradiation on the influx and efflux of potassium in compound nerve fibers (2) to attempt to relate the radiation-induced changes in electrical activity with potassium flux and (3) to use the information obtained to gain insight into the possible cellular site (s) of radiation insult to compound nerves.