Regulation of the carotid body type-1 cell by lipid signalling pathways
<p>Despite several proposed theories, the precise mechanism underlying acute oxygen sensing in type-1 cells of the carotid body remains elusive. This thesis investigates the role of Gq- coupled receptors and PLC signalling molecules in the regulation of carotid body type-1 cells by utilizing C...
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| Format: | Thesis |
| Language: | English |
| Published: |
2023
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| _version_ | 1826312214948085760 |
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| author | Alsahafi, Z |
| author2 | Buckler, K |
| author_facet | Buckler, K Alsahafi, Z |
| author_sort | Alsahafi, Z |
| collection | OXFORD |
| description | <p>Despite several proposed theories, the precise mechanism underlying acute oxygen sensing in type-1 cells of the carotid body remains elusive. This thesis investigates the role of Gq- coupled receptors and PLC signalling molecules in the regulation of carotid body type-1 cells by utilizing Ca2+ measurements and single channel electrophysiology. This thesis investigates the involvement of these signalling molecules in hypoxia-induced [Ca2+]i rise and TASK channel inhibition in type-1 cells. In addition, this thesis examines the role of PLC signalling molecules in mediating the effects of metabolic poisons and volatile anaesthetics on TASK channels in type-1 cells. This thesis seeks to address the question as to whether there might be a common signalling pathway mediating all these effects. Specifically, it proposes that lipid signalling may ultimately be central to all these forms of TASK channel regulation.</p>
<p>Following the general introduction and methods chapters, chapter 3 examines the effects of Gq- coupled receptors and PLC signalling molecules on the hypoxia-induced [Ca2+]i rise in type-1 cell. The results show that hypoxia-induced [Ca2+]i rise was sensitive to alterations in Gq-coupled receptors and PLC-signalling molecules, suggesting that these signalling molecules are involved in mediating the hypoxia-induced [Ca2+]i rise in type-1 cells.</p>
<p>Chapter 4, further examines the role of these signalling molecules by looking at their effects on the activity of TASK channels in type-1 cells. This chapter presents novel findings demonstrating the involvement of PLC signalling molecules in mediating the hypoxic inhibition of TASK channels in type 1 cells. It proposes a model for acute oxygen sensing in these cells, incorporating findings from chapters 3 and 4.</p>
<p>Chapter 5 examines the role of PLC signalling molecules in mediating the effects of metabolic inhibitors on TASK channels. Metabolic inhibitors are known to inhibit TASK channels in type-1 cells and other cell types. We further confirmed this and showed that these effects are not likely to be mediated by PLC-produced DAG.</p>
<p>Chapter 6 examines the interactions between DAG and halothane on TASK channels in type-1 cells. We demonstrated that DiC8, a DAG analogue, induced a strong, reversible, and dose-dependent inhibition of TASK channels and inhibited the halothane-induced activation of these channels. These novel findings support the hypothesis that anaesthetics and endogenous ligands may compete for binding sites in sensitive proteins.</p>
<p>In conclusion, this thesis presents novel findings on the role of Gq-coupled receptors and PLC signalling molecules in the regulation of carotid body type-1 cells and suggests that these signalling molecules are involved in mediating the responses of type-1 cells to various endogenous and exogenous stimuli. Additionally, it posits that PLC signalling molecules establish a connection between metabolic function and the modulation of TASK channels by hypoxia in type-1 cells.</p> |
| first_indexed | 2024-03-07T08:24:12Z |
| format | Thesis |
| id | oxford-uuid:1e4b9040-201c-4140-a927-1e2bb8103f1a |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T08:24:12Z |
| publishDate | 2023 |
| record_format | dspace |
| spelling | oxford-uuid:1e4b9040-201c-4140-a927-1e2bb8103f1a2024-02-14T08:28:01ZRegulation of the carotid body type-1 cell by lipid signalling pathwaysThesishttp://purl.org/coar/resource_type/c_db06uuid:1e4b9040-201c-4140-a927-1e2bb8103f1aPhysiologyEnglishHyrax Deposit2023Alsahafi, ZBuckler, KPandit, J<p>Despite several proposed theories, the precise mechanism underlying acute oxygen sensing in type-1 cells of the carotid body remains elusive. This thesis investigates the role of Gq- coupled receptors and PLC signalling molecules in the regulation of carotid body type-1 cells by utilizing Ca2+ measurements and single channel electrophysiology. This thesis investigates the involvement of these signalling molecules in hypoxia-induced [Ca2+]i rise and TASK channel inhibition in type-1 cells. In addition, this thesis examines the role of PLC signalling molecules in mediating the effects of metabolic poisons and volatile anaesthetics on TASK channels in type-1 cells. This thesis seeks to address the question as to whether there might be a common signalling pathway mediating all these effects. Specifically, it proposes that lipid signalling may ultimately be central to all these forms of TASK channel regulation.</p> <p>Following the general introduction and methods chapters, chapter 3 examines the effects of Gq- coupled receptors and PLC signalling molecules on the hypoxia-induced [Ca2+]i rise in type-1 cell. The results show that hypoxia-induced [Ca2+]i rise was sensitive to alterations in Gq-coupled receptors and PLC-signalling molecules, suggesting that these signalling molecules are involved in mediating the hypoxia-induced [Ca2+]i rise in type-1 cells.</p> <p>Chapter 4, further examines the role of these signalling molecules by looking at their effects on the activity of TASK channels in type-1 cells. This chapter presents novel findings demonstrating the involvement of PLC signalling molecules in mediating the hypoxic inhibition of TASK channels in type 1 cells. It proposes a model for acute oxygen sensing in these cells, incorporating findings from chapters 3 and 4.</p> <p>Chapter 5 examines the role of PLC signalling molecules in mediating the effects of metabolic inhibitors on TASK channels. Metabolic inhibitors are known to inhibit TASK channels in type-1 cells and other cell types. We further confirmed this and showed that these effects are not likely to be mediated by PLC-produced DAG.</p> <p>Chapter 6 examines the interactions between DAG and halothane on TASK channels in type-1 cells. We demonstrated that DiC8, a DAG analogue, induced a strong, reversible, and dose-dependent inhibition of TASK channels and inhibited the halothane-induced activation of these channels. These novel findings support the hypothesis that anaesthetics and endogenous ligands may compete for binding sites in sensitive proteins.</p> <p>In conclusion, this thesis presents novel findings on the role of Gq-coupled receptors and PLC signalling molecules in the regulation of carotid body type-1 cells and suggests that these signalling molecules are involved in mediating the responses of type-1 cells to various endogenous and exogenous stimuli. Additionally, it posits that PLC signalling molecules establish a connection between metabolic function and the modulation of TASK channels by hypoxia in type-1 cells.</p> |
| spellingShingle | Physiology Alsahafi, Z Regulation of the carotid body type-1 cell by lipid signalling pathways |
| title | Regulation of the carotid body type-1 cell by lipid signalling pathways |
| title_full | Regulation of the carotid body type-1 cell by lipid signalling pathways |
| title_fullStr | Regulation of the carotid body type-1 cell by lipid signalling pathways |
| title_full_unstemmed | Regulation of the carotid body type-1 cell by lipid signalling pathways |
| title_short | Regulation of the carotid body type-1 cell by lipid signalling pathways |
| title_sort | regulation of the carotid body type 1 cell by lipid signalling pathways |
| topic | Physiology |
| work_keys_str_mv | AT alsahafiz regulationofthecarotidbodytype1cellbylipidsignallingpathways |