Biochemical and mechanical investigation of cardiac titin isoforms [Elektronische Ressource] / vorgelegt von Ciprian Neagoe

Aus dem Institut für Physiologie und Pathophysiologie Biochemical and mechanical investigation of cardiac titin isoforms Inauguraldissertation zur Erlangung des Doctor scientiarum humanarum (Dr. sc. hum.) der Medizinischen Fakultät Heidelberg der Ruprecht-Karls-Universität vorgelegt von Ciprian Neagoe aus Câmpina, Rumänien 2008 Dekan: Prof. Dr. med. Claus R. Bartram Doktorvater: Prof. Dr. rer. nat. Wolfgang A. Linke 4 CONTENTS Page LIST OF ABBREVIATIONS 8 1. INTRODUCTION 12 1.1 Muscle contraction and three-filament model of the sarcomere 12 1.2 Molecular structure of titin - one gene, multiple isoforms 13 1.3 Sources of I-band titin elasticity 17 1.4 Theoretical models of titin elasticity 18 1.5 Titin molecules are differentially expressed in various muscle types 20 1.6 Titin and collagen are sources of passive tension in cardiac muscle 21 1.7 Heart failure can be associated with defects in cytoskeletal proteins 22 1.8 Cardiac titin and active muscle contraction 23 2. MATERIALS AND METHODS 26 2.1 Tissue 26 2.1.1 Human heart tissue 26 2.1.2 Tissue samples and preparation of myofibrils 27 2.2 Antibodies 27 2.2.1 Primary antibodies 27 2.2.2 Secondary 2.