Cardiac muscle contraction | Anatomy2Medicine
cardiac muscle contraction mechanism

Cardiac muscle contraction

 

    • The cardiac muscle cell is composed of sarcomeres.
      • The sarcomeres, which run from Z line to Z line (MCQ)
      • composed of thick and thin filaments.
    • The thick filaments are composed of myosin, whose globular heads have actin-binding sites and ATPase activity.
    • The thin filaments are composed of three proteins: actin, tropomyosin, and tro- ponin
    • Actin is a globular protein with a myosin- binding site(MCQ)
    • Tropomyosin runs along the groove of the twisted actin strands and functions to block the myosin-binding site.
    • Troponin is a globular protein composed of a complex of three subunits; the tro- ponin C subunit binds Ca2+. (MCQ)
    • When Ca2+ is bound to troponin C, a conformational change occurs, which removes the tropomyosin inhibition of actin-myosin interaction.
    • As in skeletal muscle, contraction occurs according to the sliding filament model, which states that when cross-bridges form between myosin and actin and then break, the thick and thin filaments move past each other.
    • As a result of this crossbridge cycling, the muscle fiber produces tension.
    • The transverse (T) tubules
      • invaginate cardiac muscle cells at the Z lines(MCQ)
      • continuous with the cell membranes
      • function to carry action potentials to the cell interior.
      • The T tubules form dyads with the sarcoplasmic reticulum, which is the site of storage and release of Ca2+ for excitation-contraction coupling. (MCQ)
    • Excitation-contraction coupling
      • The cardiac action potential is initiated in the myocardial cell membrane, and the depolarization spreads to the interior of the cell via the T tubules
      • Recall that a unique feature of the cardiac action potential is its plateau (phase 2), which results from an increase in gCa and an inward Ca2+ current in which Ca2+ flows through L-type Ca2+ channels (dihydropyridine receptors) from extracellular fluid (ECF) to intracellular fluid (ICF). (MCQ)
      • Entry of Ca2+ into the myocardial cell produces an increase in intracellular Ca2+ concentration.

 

  • This increase in intracellular Ca2+ concentration is not sufficient alone to initiate contraction, but it triggers the release of more Ca2+ from stores in the sarco- plasmic reticulum through Ca2+ release channels (ryanodine receptors). (MCQ)
  • This process is called Ca2+- induced Ca2+ release, and the Ca2+ that enters during the plateau of the action potential is called the trigger Ca2+. (MCQ)

 

      • Two factors determine how much Ca2+ is released from the sarcoplasmic reticulum in this step:
        • the amount of Ca2+ previously stored
        • size of the inward Ca2+ current during the plateau of the action potential.
      • Ca2+ release from the sarcoplasmic reticulum causes the intracellular Ca2+ concentration to increase even further(MCQ)
      • Ca2+ now binds to troponin C, tropomyosin is moved out of the way, and the interaction of actin and myosin can occur. (MCQ)
      • Actin and myosin bind, cross-bridges form and then break, the thin and thick filaments move past each other, and tension is produced.
      • Cross-bridge cycling continues as long as intracellular Ca2+ concentration is high enough to occupy the Ca2+-binding sites on troponin C.
      • A critically important concept is that the magnitude of the tension developed by myocardial cells is proportional to the intracellular Ca2+ concentration. (Hence Digitalis can increase myocardial contractility)
      • Relaxation
        • occurs when Ca2+ is reaccumulated in the sarcoplasmic reticulum by the action of the Ca2+ ATPase.
        • This reaccumulation causes the intracellular Ca2+ concentration to decrease to resting levels.
        • In addition, Ca2+, which entered the cell during the plateau of the action potential, is extruded from the cell by Ca2+ ATPase and Ca2+-Na+ exchange in the sarcolemmal membrane.
        • These sarcolemmal transporters pump Ca2+ out of the cell against its electrochemical gradient, with the
          • Ca2+ ATPase using ATP directly (MCQ)
          • Ca2+-Na+ exchanger using energy from the inward Na+ gradient.
    • Contractility
      • Sympathetic nervous system.
        • Stimulation of the sympathetic nervous system have a positive inotropic effect
        • positive inotropic effect has three important features:
          • increased peak tension
          • increased rate of tension development
          • faster rate of relaxation.
        • Faster relaxation means that the contraction (twitch) is shorter, allowing more time for refilling.
        • Mechanism of positive ionotropic effect (MCQ)
          • mediated via activation of b1 receptors
          • beta 1 receptors are coupled via a Gs protein to adenylyl cyclase
          • Activation of adenylyl cyclase leads to the production of cAMP
          • cAMP causes (MCQ)
            • activation of protein kinases
            • phosphorylation of proteins that produce the physiologic effect of increased contractility.
          • Two different proteins are phosphorylated to produce the increase in contractility. these phosphorylated proteins then produce an increase in intracellular Ca2+ concentration.
            • There is phosphorylation of the sarcolemmal Ca2+ channels that carry inward Ca2+ current during the plateau of the action potential. (MCQ)
              • As a result, there is increased inward Ca2+ current during the plateau and increased trigger Ca2+, which increases the amount of Ca2+ released from the sarcoplasmic reticulum.
            • There is phosphorylation of phospholamban (MCQ)
              • a protein that regulates Ca2+ ATPase in the sarcoplasmic reticulum.
              • When phosphorylated, phospholamban stimulates the Ca2+ ATPase, resulting in greater uptake and storage of Ca2+ by the sarcoplasmic reticulum.
      • Parasympathetic nervous system.
      • have a negative inotropic effect on the atria.
      • This effect is mediated via muscarinic receptors, which are coupled via a Gi protein called GK to adenylyl cyclase. (MCQ)
      • Because the G protein in this case is inhibitory, contractility is decreased (opposite of the effect of activation of beta1 receptors by catecholamines).
      • Two factors are responsible for the decrease in atrial contractility caused by parasympathetic stimulation. (MCQ)
        • ACh decreases inward Ca2+ current during the plateau of the action potential.
        • ACh increases IK-ACh, (constitutively active, acetylcholine-regulated K+-current (IK,ACh) )thereby shortening the duration of action potential and, indirectly, decreasing the inward Ca2+ current (by shortening the plateau phase).
    • Effect of Heart Rate on Contractility
      • When the heart rate increases, contractility increases
      • When the heart rate decreases, contractility decreases.

 

  • Mechanism

 

        • When heart rate increases, there are more action potentials per unit time and an increase in the total amount of trigger Ca2+ that enters the cell during the plateau phases of the action potentials.
          • if the increase in heart rate is caused by sympathetic stimulation or by catecholamines, then the size of the inward Ca2+ current with each action potential also is increased. (MCQ)
        • Because there is greater influx of Ca2+ into the cell during the action potentials, the sarcoplasmic reticulum accumulates more Ca2+ for subsequent release (i.e., increased stored Ca2+).
          • if the increase in heart rate is caused by sympathetic stimulation, then phospholamban, which augments Ca2+ uptake by the sarcoplasmic reticulum, will be phosphorylated, further increasing the uptake process.
      • Two specific examples of the effect of heart rate on contractility, the positive staircase effect and postextrasystolic potentiation,

 

  • Positive staircase effect. (MCQ)

 

        • The positive staircase effect is also called the Bowditch staircase, or Treppe (MCQ)
        • When heart rate doubles, for example, the tension developed on each beat increases in a stepwise fashion to a maximal value
        • This increase in tension occurs because there are more action potentials per unit time, more total Ca2+ entering the cell during the plateau phases, and more Ca2+ for accumulation by the sarcoplasmic reticulum (i.e., more stored Ca2+).  
        • Notice that the very first beat after the increase in heart rate shows no increase in tension because extra Ca2+ has not yet accumulated
        • On subsequent beats, the effect of the extra accumulation of Ca2+ by the sar- coplasmic reticulum becomes evident.
        • Tension rises stepwise, like a staircase
        • With each beat, more Ca2+ is accumulated by the sarcoplasmic reticulum, until a maximum storage level is achieved.