| Abstract | 第6-7页 |
| 中文摘要 | 第8-11页 |
| Abbreviations/Acronyms | 第11-14页 |
| Chapter Ⅰ A Brief Review:Smooth muscle signal transduction in health and disease | 第14-56页 |
| 1. Characteristics of smooth muscle and its physiological function | 第14-20页 |
| 1.1 Structure of smooth muscle | 第16-19页 |
| 1.1.1 Actin thin filaments | 第16-17页 |
| 1.1.2 Myosin thick filaments | 第17-18页 |
| 1.1.3 Intermediate filaments | 第18页 |
| 1.1.4 Other proteins of the contractile apparatus | 第18-19页 |
| 1.2 Smooth muscle phenotype switch | 第19-20页 |
| 2. Mechanisms of smooth muscle contraction | 第20-42页 |
| 2.1 Excitation-contraction coupling and Ca~(2+) movements | 第23-25页 |
| 2.1.1 Electromechanical coupling | 第23-24页 |
| 2.1.2 Pharmacomechanical coupling | 第24页 |
| 2.1.3 Ca~(2+)movements | 第24-25页 |
| 2.2 Kinases and regulatory light chain phosphorylation | 第25-32页 |
| 2.2.1 Dependence of force and RLC phosphorylation | 第26页 |
| 2.2.2 RLC phosphorylation by Ca~(2+) dependent MLCK | 第26-28页 |
| 2.2.3 RLC phosphotylation by Ca~(2+) independent kinase | 第28-32页 |
| 2.3 Phosphatase and regulation of Ca~(2+) sensitivity | 第32-42页 |
| 2.3.1 Myosin light chain phosphatease | 第33-38页 |
| 2.3.2 Ca~(2+) sensitivity | 第38-42页 |
| 3. Smooth muscle in disease states | 第42-44页 |
| 4. References | 第44-56页 |
| Chapter Ⅱ Constitutive phosphorylation of MYPT1 Thr694 regulates force maintenance ofsmooth muscle | 第56-87页 |
| 1. Summary | 第57页 |
| 2. Introduction | 第57-59页 |
| 3. Materials and Methods | 第59-65页 |
| 3.1 Generation of Mypt1 mutant(T694A)mice | 第59-60页 |
| 3.2 Genotyping of mice | 第60-61页 |
| 3.3 Chemicals and antibodies | 第61页 |
| 3.4 Preparation of mouse embryonic fibroblasts(MEFs) | 第61页 |
| 3.5 Karyotyping analysis | 第61-62页 |
| 3.6 Animals and tissues preparation | 第62页 |
| 3.7 Analysis of smooth muscle contractility | 第62-63页 |
| 3.8 Protein sample preparation and Western blotting assay | 第63-64页 |
| 3.9 Histology | 第64页 |
| 3.10 Data analysis | 第64-65页 |
| 4. Results | 第65-81页 |
| 4.1 Characterization of dynamic phosphorylation of MYPT1 in bladder smooth muscle | 第65-67页 |
| 4.2 Generation and characterization of Myptl knock-in mice(T694A) | 第67-74页 |
| 4.3 T694A mutant smooth muscle displayed reduced sustained force | 第74-76页 |
| 4.4 T694A mutation reduces RLC phosphorylation at sustained phase | 第76-79页 |
| 4.5 Force regulation by MYPT1 T694 phosphorylation is independent of ROCK and PKC signaling | 第79-81页 |
| 4.6 ZIPK is not the native kinase for MYPT1 Thr694 | 第81页 |
| 5. Discussion | 第81-84页 |
| 6. References | 第84-87页 |
| Chapter Ⅲ Inducible Thr852 phosphorylation is not necessary for smooth musclecontraction | 第87-116页 |
| 1. Summary | 第88页 |
| 2. Introduction | 第88-90页 |
| 3. Materials and Methods | 第90-95页 |
| 3.1 Generation of Mypt1 mutant(T852A)mice | 第90页 |
| 3.2 Genotyping of mice | 第90-91页 |
| 3.3 Chemicals and antibodies | 第91页 |
| 3.4 Animals and tissues preparation | 第91-92页 |
| 3.5 Bladder smooth muscle contractility | 第92页 |
| 3.6 Aortic artery contractility | 第92-93页 |
| 3.7 Protein sample preparation and western blot assay | 第93-94页 |
| 3.8 Histology | 第94-95页 |
| 3.9 Data analysis | 第95页 |
| 4. Results | 第95-111页 |
| 4.1 Generation of Myptl knock-in mice(T852A) | 第95-102页 |
| 4.2 T852A did not apparently affect contractile behaviors and RLC phosphorylation in bladder smooth muscle | 第102-106页 |
| 4.3 Thr852 phosphorylation is not necessary for phasic smooth muscle | 第106-107页 |
| 4.4 Thr852 phosphorylation is not required for tonic smooth muscle contraction(aorta) | 第107-108页 |
| 4.5 T852A mutation doesn't resist to ROCK inhibitor | 第108-111页 |
| 5. Discussion | 第111-114页 |
| 6. References | 第114-116页 |
| 致谢 | 第116-118页 |
| Publications | 第118-120页 |
