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On the effect of physiological acidosis in hibernating rodents Kim, Anne
Abstract
Metabolic rate suppression during hibernation requires an orchestrated global reduction in metabolism while still matching O₂ supply and demand. Acidosis has been suggested as a mechanism for suppressing metabolic rate in hibernation, although the mechanism behind this process has not been thoroughly investigated. Findings from my thesis indicate that hemoglobin of both the facultative hibernator (Syrian hamster) and the obligate hibernator (13-lined ground squirrel) exhibit a reduced temperature sensitivity and increased Bohr effect relative to the non-hibernating rat, ultimately enhancing O₂ offloading at the tissues. I also found that in the obligate hibernator, due to metabolic state-dependent changes in intracellular buffering constituents, the ionisation ratio of intracellular imidazole (αim) did not vary between euthermia and hibernation. In the facultative hibernator, αim remained constant regardless of hibernation state. These findings contradict previous speculation that acidosis may suppress metabolism in quiescent tissues such as the brain and skeletal muscle during hibernation. Furthermore, mitochondrial respiration increased at low pH despite the reduced activity of electron transport system (ETS) enzymes at low pH. This suggests that, despite ETS enzyme activity being reduced at low pH, acidosis may reverse the inhibitory mechanisms that suppress mitochondrial respiration during steady-state hibernation, leading to the observed increase in mitochondrial respiration at low pH. Lastly, acidosis decreased cellular ATPase activity in the hibernating species but not in the rat. In the obligate hibernator, this inhibitory effect of acidosis on cellular ATPase activity was present regardless of hibernation state and assay temperature (37 – 10 °C). In the facultative hibernator, the effect of acidosis on ATPase activity was only present during euthermia and at warm temperatures. Taken together, these findings indicate that acidosis does not occur in quiescent tissues of hibernators or lower mitochondrial O₂ consumption. Instead, it may serve a role in matching O₂ supply to the high O₂ demand during arousal by increasing O₂ offloading by hemoglobin. Collectively, these data provide novel insight into the role of acidosis during hibernation that were previously uncharacterised.
Item Metadata
Title |
On the effect of physiological acidosis in hibernating rodents
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Creator | |
Supervisor | |
Publisher |
University of British Columbia
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Date Issued |
2023
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Description |
Metabolic rate suppression during hibernation requires an orchestrated global reduction in metabolism while still matching O₂ supply and demand. Acidosis has been suggested as a mechanism for suppressing metabolic rate in hibernation, although the mechanism behind this process has not been thoroughly investigated. Findings from my thesis indicate that hemoglobin of both the facultative hibernator (Syrian hamster) and the obligate hibernator (13-lined ground squirrel) exhibit a reduced temperature sensitivity and increased Bohr effect relative to the non-hibernating rat, ultimately enhancing O₂ offloading at the tissues. I also found that in the obligate hibernator, due to metabolic state-dependent changes in intracellular buffering constituents, the ionisation ratio of intracellular imidazole (αim) did not vary between euthermia and hibernation. In the facultative hibernator, αim remained constant regardless of hibernation state. These findings contradict previous speculation that acidosis may suppress metabolism in quiescent tissues such as the brain and skeletal muscle during hibernation. Furthermore, mitochondrial respiration increased at low pH despite the reduced activity of electron transport system (ETS) enzymes at low pH. This suggests that, despite ETS enzyme activity being reduced at low pH, acidosis may reverse the inhibitory mechanisms that suppress mitochondrial respiration during steady-state hibernation, leading to the observed increase in mitochondrial respiration at low pH. Lastly, acidosis decreased cellular ATPase activity in the hibernating species but not in the rat. In the obligate hibernator, this inhibitory effect of acidosis on cellular ATPase activity was present regardless of hibernation state and assay temperature (37 – 10 °C). In the facultative hibernator, the effect of acidosis on ATPase activity was only present during euthermia and at warm temperatures. Taken together, these findings indicate that acidosis does not occur in quiescent tissues of hibernators or lower mitochondrial O₂ consumption. Instead, it may serve a role in matching O₂ supply to the high O₂ demand during arousal by increasing O₂ offloading by hemoglobin. Collectively, these data provide novel insight into the role of acidosis during hibernation that were previously uncharacterised.
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Genre | |
Type | |
Language |
eng
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Date Available |
2023-04-06
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Provider |
Vancouver : University of British Columbia Library
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Rights |
Attribution-NonCommercial-NoDerivatives 4.0 International
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DOI |
10.14288/1.0430329
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URI | |
Degree | |
Program | |
Affiliation | |
Degree Grantor |
University of British Columbia
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Graduation Date |
2023-05
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Campus | |
Scholarly Level |
Graduate
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Rights URI | |
Aggregated Source Repository |
DSpace
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Rights
Attribution-NonCommercial-NoDerivatives 4.0 International