Sphingomyelin (SM), a sphingolipid that is concentrated in the extracellular leaflet of the plasma membrane, can interact with cholesterol to form more ordered raft domains. The hydrolysis of SM by sphingomyelinase (SMase) generates ceramide and may redistribute cholesterol molecules to other less ordered domains. I employed carbon fibre amperometry to examine whether SM hydrolysis affected the kinetics of release of catecholamines from individual granules of rat chromaffin cells when exocytosis was triggered by elevated extracellular [K+]. Similar to cholesterol overload, SMase treatment selectively increased the proportion of stand-alone foot signals and the duration of the pre-spike foot signals; both effects could be reduced by extraction of cellular cholesterol. In contrast, the application of an exogenous ceramide did not mimic the effects of SMase. My results suggest that SMase treatment liberated cholesterol from lipid rafts to increase the persistence of the semi-stable fusion pore before the onset of rapid dilation.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:AEU.10048/1230 |
| Date | 11 1900 |
| Creators | Yin, Jihuan |
| Contributors | Tse, Fred (Pharmacology), Tse, Amy (Pharmacology), Smith, Peter (Pharmacology), Baker, Glen (Psychiatry) |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | 1693852 bytes, application/pdf |
Page generated in 0.002 seconds