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PROTON TRANSPORT GROUP |
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Research |
RESEARCH INTERESTS
Regulation of Intracellular pH in heart
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Local intracellular control of pHi It has become apparent that pHi is controlled locally within the cardiac cell. This is because, intracellular proton mobility within cytoplasm is very low, more than 200 fold lower than proton mobility in water. Low H+ mobility is a direct consequence of the high levels of intracellular buffers, many of which are, themselves, poorly mobile. As a result, localised intracellular acid or base loads can take many seconds to dissipate diffusively. The pHi can therefore become spatially non-uniform, leading to the generation of pHi microdomains. We are investigating the mechanism responsible for regulating proton mobility within the cardiac myocyte, including the role played by the CO2/HCO3- buffer system and the endogenous enzyme carbonic anhydrase. We are also investigating circumstances that lead to spatial non-uniformity of pHi, such as stimulation of sarcolemmal acid transport or localised exposure of myocardial cells to membrane permeant weak acids or bases. A dramatic example of this is exposure of a ventricular cell to an extracellular gradient of pCO2, such as may occur across an ischaemic border zone in the myocardium. This leads to a major standing gradient of intracellular pH that can be as large as 1.0 units. |
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To read more about our research please click on the titles below: |
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Local intracellular control of pHi |