Homeostatic control of pH is vital to normal bodily function. We are interested in examining the mechanisms by which neurones detect pH changes and focus on two main areas, pain and control of breathing: 1) A subset of sensory neurones detects purely noxious stimuli, so-called nociceptors, but how they are activated by acid is not fully understood. Painful inflammatory conditions, such as rheumatoid arthritis, are associated with tissue acidosis, which is likely a key component in driving pain. We use a combination of molecular biology, immunohistochemistry, neuronal tracing, animal models and whole-cell electrophysiology techniques to examine: how nociceptors respond to acid, the nature of the ion channels involved and the impact of inflammation upon nociceptor excitability. 2) Changes in CO2 concentration modulate breathing, possibly due to CO2-evoked changes in pH. The naked mole-rat has adapted to living in a high CO2/low O2 environment and we will employ a comparative physiology/genetics approach to learn how naked mole-rats are adapted to living in such extreme conditions; techniques include: behavioural work, immunohistochemistry, electrophysiology and real-time fluorescence imaging. By understanding how organisms are adapted to living in extreme conditions it is possible to learn more about how organisms living in “normal” conditions function and by focusing on breathing circuits we aim to shed light on the aberrant CO2-sensitivity observed in several respiratory pathologies. Techniques used include: whole-cell electrophysiology, neuronal tracing, molecular biology (RT-PCR, mutagenesis etc.), cell culture, transfection, immunohistochemistry and behavioural work. Key words: pain, nociception, acid, neurobiology, ion channels, breathing, chemoreception
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