• A 64-year-old man with chronic obstructive pulmonary disease presents with palpitations and lightheadedness. In his chart, there are documented allergies to calcium channel blockers. He is tachycardic (160/min). An electrocardiogram reveals an irregular supraventricular rhythm with polymorphic P waves. A medication that increases contractility is given. (Digoxin)
  • Generation of action potential
    • initiated by the sinoatrial (SA) node
    • delayed by the atrioventricular (AV) node
      • allows for ventricular filling prior to contraction
  • Excitability and refractory periods
    • excitability
      • myocytes are able to generate an action potential in response to depolarization
      • cells must reach the threshold potential to achieve an action potential
    • refractory period
      • occurs after depolarization
      • prevents further depolarization as the inactivation gates on the Na+ channels are closed and no current can flow through them
      • once a cell is repolarized, the inactivation gates on the Na+ channels re-open
        • a cell is once again excitable
Excitation-Contraction Coupling
  • The action potential causes a rush of Ca2+ into the cell
    • via L-type voltage-gated Ca2+ channels (dihydropyridine receptors)
      • indirectly blocked by β-blockers via ↓ cAMP
      • directly blocked by dihydropyridine Ca2+ channel blockers
  • This triggers the release of more Ca2+ from the sarcoplasmic reticulum
    • via ryanodine receptors
      • blocked by the ryanodine toxin
  • Ca2+ binds to troponin C
    • tropomyosin is moved out of the way
  • Actin and myosin can now bind
    • cross-bridges are formed and broken, and thin and thick filaments slide past each other creating tension
  • Contraction occurs
  • Contractility, or level of tension generated, is determined by intracellular Ca2+
    • positive inotropic agents increase intracellular Ca2+
    • digoxin
      • inhibits extracellular K+ binding site of the Na+-K+ ATPase on myocyte cell membrane
        • when the ATPase is inhibited, ↑ Na+ intracellular concentration
        • Ca2+-Na+ exchanger decreases the amount of Ca2+ it pumps out of the cell
        • ↑ Ca2+ intracellular concentration
  • Relaxation and repolarization of the cell membrane occurs when ↓ intracellular Ca2+ concentration back to resting levels 
    • Ca2+ ATPase on sarcoplasmic reticulum membrane
      • Ca2+ returns to sarcoplasmic reticulum
    • Ca2+ ATPase on cell membrane
      • Ca2+ extruded out of the cell
    • Ca2+-Na+ exchange on cell membrane
      • exchanges 1 Ca2+ out of the cell for 3 Na+ into the cell

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