g1bh 2012 2013 hc-13-14 - contractie mechanismen 1 en 2 - steendijk
TRANSCRIPT
G1BH 2012-2013 - HC-13 en HC-14
Cardiac mechanics
Paul Steendijk, PhD
Associate Professor Cardiovascular PhysiologyDepartment of Cardiology, LUMC
2013.02.13
Contraction mechanisms
Excitation-contraction
Pump function
Electrical activation
Anatomy & geometry
Cardiovascular interactions & loading conditions
Neurohormonal systems
Determinants of cardiac function
Cardiac mechanics
Contraction mechanisms
Excitation-contraction coupling
Pump function (+ PV loops)
Literature
• Medical Physiology - Boron & Boulpaep• Cardiovascular Physiology Concepts – Klabunde• Heart Disease – Braunwald• Cardiovascular Medicine - Camm
myofilaments:contractile proteins
myofibers
myofibrils
myocardium: beating heart
~20x100 µm ~2 µm
~1-10cm
From the sarcomere to the heartFrom shortening to ejection
myocytes
sarcomeres: contractile units
10-6 m
~10 nm
10-8 m 10-4 m 10-2 m
Cardiac muscle, coloured TEM
Contractile proteins
Contractile proteins, transverse section
Contractile proteins, transverse section
Myofilament interaction (sliding filaments)
Crossbridge cycling – power stroke
Crossbridge cycling
Sarcomere, contraction-relaxation
Myosin
300-400 myosin molecules, 460kD
Head region, ATP and actin binding sites
Cross-bridges, every 14.3nm, 600 angle
Thick filament (Myosin)
Actine, globular protein, 44kD, 5.5nm
Tropomyosin
Troponine complex, regulatory
Thin filament (Actin)
Actin-Myosin interaction
Myosin, ATP dependent motor proteins
Myosin V, movement along an actin filament
Spudich - Nature Reviews Molecular Cell Biology 2001
Molecular motors
Actin-Myosin & Titin
Isotonic contraction:force development and shortening
Isometric contraction:maximal force development, no shortening
C
B
D
Peak isometric force is length-dependent
©1999 by American Physiological Society
Force-length relationship
Peak Isometric Force-Length relationship
Landesberg et al. Am J Physiol Heart Circ Physiol 1999;276:H998-H1011
©1999 by American Physiological Society
Force-length relationship
Peak Isometric Force-Length relationship
Landesberg et al. Am J Physiol Heart Circ Physiol 1999;276:H998-H1011
Passive Force-Length relationship
Isometric and isotonic contractions
AFTERLOAD
PRELOAD
Actin – Myosin overlap
Sarcomere Force-Length relationship
Possible mechanisms Frank-Starling Relationship
Starling: “Law of the Heart”(Linacre Lecture, 1915)Increased sarcomere length >>> Increased force of contraction
Possible mechanisms:- Optimal actin-myosin overlap- Reduced lattice spacing- Altered myosin head orientation- Increased Ca sensitivity