兴奋收缩耦联和心力衰竭的治疗.ppt

田野 教授 哈医大二院心内科 TOPICS Excitation-contraction (EC) coupling Excitation Calcium Cycling Contraction Alterations of E-C coupling in HF Inotropic agents for HF Excitation-contraction coupling  He was an English medical doctor /physician, who is credited with being the first to correctly describe, in exact detail, the systemic circulation and properties of blood being pumped around the body by the heart. We shall designate the entire seque-nce of reactions: excitation, inward acting link, and activation of contra-ction by the term excitation-contraction coupling. Cardiac excitation–contraction coupling is the process from electrical excitation of the myocyte to contraction of the heart (which propels blood out). The ubiquitous second messenger Ca2+ is essential in cardiac electrical activity and is the direct activator of the myofilaments, which cause contraction. Excitation The cardiac action potential A notable difference between skeletal and cardiac myocytes is how each elevates the myoplasmic Ca2+ to induce contraction. In cardiac myocytes, the release of Ca2+ from the sarcoplasmic reticulum is induced by Ca2+ influx into the cell through voltage-gated calcium channels. Calcium Cycling  Pictorial OF Calcium Cycling Cardiac tissue and cells Sarcoplasmic Reticulum(SR) PLN and SERCA Sodium-calcium exchanger(NCX) Two-way transporter “forward”mode “reverse”mode Na:Ca=3:1 Contraction  Sliding Filament Theory EM evidence for sliding filament theory The molecular basis for myocardial contraction Thick Filament Proteins Myosin Head (S1) – molecular motor of muscle contraction G-Actin F-Actin Crystal Structure of Human Cardiac Troponin Regulation of thin filament in contraction Muscle Contraction Alterations in E-C coupling in HF RyR2 channel leak PLN–SERCA2a interactions in physiological and diseased cardiac function Inotropic Agents for HF Inotropic Agents and β-blocker Digitalis Phosphodiesterase inhibitor β- adrenoceptor