Format:
Online-Ressource (XVII, 217 p. 102 illus., 38 illus. in color, online resource)
ISBN:
9783319072005
Series Statement:
Springer Theses, Recognizing Outstanding Ph.D. Research
Content:
The Short QT Syndrome (SQTS) is characterized by abbreviated QT intervals on the electrocardiogram, increased risk of cardiac arrhythmias and sudden death. Although several gene mutations have been identified in SQT patients, the role of these mutations in promoting arrhythmogenesis is still not completely understood. Consequently, this thesis employs multidisciplinary approaches to develop a 3D virtual heart, which is then used to elucidate how the short QT syndrome facilitates and maintains ventricular arrhythmias and to determine its effects on ventricular mechanical contraction. The findings in this thesis provide a comprehensive and mechanistic explanation for a number of gene mutations associated with potassium channels in terms of susceptibility to arrhythmia. The multiphysics models developed provide a powerful platform for identifying the root causes of various arrhythmias and investigating therapeutic interventions for these diseases. The thesis was examined by Prof. Chris Huang of the University of Cambridge, the most authoritative figure in cardiac electrophysiology, who has described the work as “outstanding.”
Note:
Description based upon print version of record
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Supervisor's Foreword; Abstract; Acknowledgments; Contents; 1 Introduction to Ion Channels and the Cardiac Action Potential; 1.1…The Cardiac Action Potential; 1.2…Morphology of the Action Potential in Different Parts of the Heart; 1.2.1 Sinoatrial Node; 1.2.2 Atria; 1.2.3 Atrioventricular Node; 1.2.4 His Bundle Purkinje System; 1.2.5 Ventricle; 1.3…Ionic Basis of Resting and Action Potential; 1.3.1 The Uniformly Polarised Cell; 1.3.2 Electrical Equivalent Circuit of a Cell; 1.3.3 Equilibrium Potential; 1.4…Properties of Ion Channels; 1.4.1 Ion Permeation; 1.4.2 Gating; 1.5…Sodium Channels
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1.6…Calcium Channels1.6.1 L-Type Calcium Channel; 1.6.2 T-Type Calcium Channel; 1.7…Potassium Channels; 1.7.1 Voltage-Dependent K+ Channels; 1.7.1.1 The Transient Outward Current (Ito); 1.7.1.2 The Slowly-Activated Delayed Outward Rectifier Current (IKs); 1.7.1.3 The Rapidly-Activated Delayed Outward Rectifier Current (IKr); 1.7.1.4 The Ultrarapidly-Activated Delayed Outward Rectifier Current (IKur); 1.7.2 Inward Rectifier Potassium Channels; 1.7.2.1 The Inward Rectifier K+ Current (IK1); 1.7.2.2 Acetylcholine-Activated K+ Channel (IK,Ach); 1.7.2.3 ATP-Senstitve K+ Channel (IK,ATP)
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1.8…Stretch-Activated Channels1.9…Cardiac Muscle Contraction; 1.9.1 Cardiac Muscle Fibre; 1.9.1.1 Myofibrils; Actin and Myosin Filaments; 1.9.1.2 Sarcoplasm, Transverse Tubule and Sarcoplasmic Reticulum and the General Mechanism of Contraction; 1.9.2 Molecular Mechanism of Contraction; 1.9.2.1 Myosin Filament; 1.9.2.2 Actin Filament; 1.9.2.3 Cross-Bridge Cycling or The ''Walk-Along'' Theory of Contraction; 1.9.2.4 The Source of Energy for Contraction: ATP; References; 2 Potassium Channels Implicated in the Short QT Syndrome; 2.1…Rectification; 2.2…The hERG/IKr Potassium Channel
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2.2.1 hERG/IKr Potassium Channel Gating2.2.2 hERG/IKr Channel Structure; 2.3…The KCNQ1-KCNE1/IKs Potassium Channel; 2.3.1 KCNQ1-KCNE1/IKs Potassium Channel Gating; 2.3.2 KCNQ1-KCNE1/IKs Channel Structure; 2.4…The KCNJ2/IK1 Potassium Channel; 2.4.1 Kir2.1/IK1 Potassium Channel Gating; 2.4.2 KCNJ2/IK1 Channel Structure; 2.5…Current Profiles During an Action Potential; References; 3 The Short QT Syndrome; 3.1…Introduction; 3.2…SQT1 and KCNH2; 3.3…SQT2 and KCNQ1; 3.4…SQT3 and KCNJ2; 3.5…SQT4 and SQT5; 3.6…Current Treatment of SQT Patients; References; 4 Model Development
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4.1…Modelling Voltage-dependent Channels: Hodgkin--Huxley Versus Markov Chain Models4.1.1 The Hodgkin--Huxley Formalism; 4.1.1.1 The Complete Hodgkin-Huxley Model; 4.1.2 Markov Chain Models; 4.2…Development of the SQT1 Markov Model; 4.2.1 The Base IKr Markov Model; 4.2.2 The SQT1 Markov Model; 4.2.2.1 WT; 4.2.2.2 N588K; 4.3…Development of the SQT2 Markov Model; 4.3.1 The Base IKs Markov Model; 4.3.2 The SQT2 Markov Model; 4.3.2.1 WT; 4.3.2.2 V307L; 4.4…Development of the SQT3 Hodgkin--Huxley Model; 4.4.1 The Base IK1 Model; 4.4.2 The SQT3 Hodgkin--Huxley Model; 4.4.2.1 WT; 4.4.2.2 WT-D172N
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4.4.2.3 D172N
Additional Edition:
ISBN 9783319071992
Additional Edition:
Erscheint auch als Druck-Ausgabe ISBN 978-331-90719-9-2
Language:
English
Keywords:
Hochschulschrift
DOI:
10.1007/978-3-319-07200-5
URL:
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