Cardiac Myocyte Physiology

Snapshot

• 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)

Introduction

• 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
    • note, myocytes are electrically coupled via gap junctions that allow propagation of the 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 
    • indirectly blocked by β-blockers via ↓ cAMP
    • directly blocked by non-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

• 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

• 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