Cardiac Physiology V

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Cardiac Physiology(V)

• A. Rüçhan Akar
• Ankara University
• School of Medicine
• December- 2003

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Contraction-relaxation Cycle
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Ventricular myocyte action potential
Ferrari R, Opie LH, 1992 Atlas of the
myocardium Raven Press Ltd.
Phase 0 rapid depolarisation (Na in) Phase 1
brief early repolarisation Phase 2 plateau (Ca
2 in) Phase 3 rapid repolarisation (K
out) Phase 4 resting membrane potential
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• Phases 0 and 1
• Opening of fast sodium channels
• Closure of potassium channels
• Phase 2
• Calcium entry through L-type calcium channels
• Phase 3
• Reopening of potassium channels
• Phase 4
• Equilibrium potential for potassium

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• Cardiac Muscle
• Action potential duration 300 msec
• Plateau phase prolongs the active state
• Nerve or skeletal muscle
• Action potential duration 1 msec

Cranefield PF. Circ. Res. 1977 41, 415-423
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Contraction-relaxation CycleContractile Proteins

• thin actin filament
• thick myosin filament
• titin (connectin) is a newly discovered large
  elastic molecule that supports myosin

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sarcomere basic contractile unit within the
myocyte
Actin
Myosin Filamentous tail Globular head
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Actin filament- two helical chains Tropomyosin
the backbone of two helical actin chains At
certain intervals the protein complex troponin is
bound to the actin Troponin consists three
componentsTnI,TnC,TnT
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Titin (Connectin)

• the largest protein molecule yet described
• acts as a third filament and provides elasticity
• two distinct segments
• inextensible segment that interacts with myosin
  (tethers the myosin molecule to the Z line)
• extensible segment that stretches as sarcomere
  length increases

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Contraction-relaxation Cycle
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Contraction

• action potential
• release of Ca2 from SR store
• actin-myosin sliding filament mechanism (no
  shortening of individual molecules)
• sarcomere shortens (closer Z lines)
• ATP supplied by the mitochondria

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Cardiac Muscle and Action Potential

• the entry of relatively small amounts of Ca2
  into the myocyte during early plateau triggers
  the release of a larger amount of Ca2 from SR
  (internal store)
• some of the Ca2 binds to troponin-C on the thin
  actin filaments, leading to exposure of myosin
  binding sites
• Actin-myosin cross-bridges

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Ca2 release from SR
Ca2 ions bind to troponin C
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Myosin head flexes, Cross-links to the actin
ATP attaches to myosin head, head extends
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The Strength of ContractionInotropic State

• related to the Ca2 fluxes
• any manipulation that leads to an enhanced
  cytosolic Ca2 during systole will increase
  inotropic state (occupy more troponin C-binding
  sites)
• generation of greater force for any given length

Sperelakis N, Kurachi Y, Terzic A, Cohen
MV. Heart Physiology and Pathophysiology Academic
Press, 2001
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Active Relaxation

• dependent on the function of SERCA-2
• 1 mol ATP for 2 mol Ca2 (transport back to SR)
• other systems for removal of Ca2 from cytosol
• Na/Ca2 exchanger (three Na ions for one Ca2)
• Sarcolemmal Ca2 ATPase
• Cytosolic Ca2 binding proteins (calmodulin and
  calsequestrin)