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