摘要 | 第4-5页 |
Abstract | 第5页 |
Chapter Ⅰ Introduction | 第8-25页 |
1.1 Cardiac voltage-gated sodium channel (Nav) | 第8-13页 |
1.1.1 Background | 第8-9页 |
1.1.2 Na_v 1.5/alpha (a) subunit of Cardiac Na_v channel | 第9-12页 |
1.1.3 Beta (β) subunit of cardiac Na_v channel | 第12-13页 |
1.2 Small GTP-binding proteins/small GTPases | 第13-20页 |
1.2.1 Background | 第13页 |
1.2.2 Molecular Switches and the Activation-Inactivation Cycle | 第13-14页 |
1.2.3 Regulators of Small GTPase | 第14-16页 |
1.2.4 Types of Small GTPases and their Functions | 第16-20页 |
1.3 Regulation of Vesicular Transport by Sarl/Arf Proteins | 第20-25页 |
1.3.1 Vesicle Trafficking | 第20-21页 |
1.3.2 Sar1 Protein and Vesicular Transport | 第21-22页 |
1.3.3 Arf Protein and Vesicular Transport | 第22-23页 |
1.3.4 Impaired Trafficking & SCN5A gene mutation | 第23-25页 |
Chapter Ⅱ Materials and Methods | 第25-40页 |
2.1 Materials | 第25-30页 |
2.1.1 Reagents and Suppliers | 第25-26页 |
2.1.2 Reagents Preparation methods | 第26-29页 |
2.1.3 Instruments and Suppliers | 第29-30页 |
2.2 Methods | 第30-40页 |
2.2.1 Transfection | 第30-32页 |
2.2.2 Protein Extraction | 第32-34页 |
2.2.3 Western Blot | 第34-38页 |
2.2.4 Confocal Microscopy | 第38-40页 |
Chapter Ⅲ Results & Analysis | 第40-49页 |
3.1 Sar1 Regulates Na_v1.5 trafficking from the ER to the Golg | 第40-46页 |
3.1.1 Mutant Sar1 reduces Na_v1.5 expression of both total cell lysateand cell membrane (demonstrated by Western blot) | 第40-43页 |
3.1.2 Mutant Sar1 reduces localization of Na_v1.5 at the cell surface(demonstrated by Confocal microscopy) | 第43-46页 |
3.2 Effect of Arf in Na_v1.5 Regulation is relatively small | 第46-49页 |
3.2.1 Na_v1.5 Expression is NOT affected significantly byMutant Q71L-Arf1(demonstrated by Western blot) | 第46-48页 |
3.2.2 Mutant Arf does NOT significantly reduce the localization ofNa_v1.5 at the cell surface (demonstrated by Confocal microscopy) | 第48-49页 |
Chapter Ⅳ Discussion & Future Perspectives | 第49-51页 |
References | 第51-64页 |
Abbreviations | 第64-65页 |