Myocardial Action Potential

Snapshot

• A 60-year-old man presents to his cardiologist for a follow-up of newly diagnosed diastolic heart failure. He has a history of asthma and chronic obstructive lung disease. He reports that his pulmonologist does not want him to take β-blockers. However, his cardiologist wants to start him on a medication to slow the heart rate. He reassures the patient that this drug acts not on β-receptors but on a Ca²⁺ channel. (Verapamil)

Introduction

• Ions responsible for the action potential of atria, ventricles, and Purkinje fibers are the same
  • upstroke
    • inward Na⁺ current
  • plateau
    • slow inward Ca²⁺ current via L-type voltage-gated Ca²⁺ channels
    • a sustained period of depolarization
• allows for ventricular filling

Ventricular Action Potential

• Resting membrane potential 
  • -85 mV resting membrane potential is maintained by inward rectifier K⁺ channels
    • inward rectifier K⁺ channels open at rest and close with depolarization
• Phase 0, upstroke 
  • rapid depolarization
    • caused by the opening of voltage-gated Na⁺ channels and inward Na⁺ current
      • Na⁺ current depolarizes cell membrane, which closes inward rectifier K⁺ channels
• Phase 1, initial repolarization
  • brief repolarization and net outward current
    • inactivation gates on Na⁺ channels close
    • Na⁺ current is decreased
    • outward K⁺ current down an electrochemical gradient
• Phase 2, plateau 
  • stable, long period of depolarized membrane potential
  • inward and outward current are equal, with no net current flow
    • inward Ca²⁺ current (slow inward current)
      • opened L-type Ca²⁺ channels
        • blocked by Ca²⁺ channel blockers
      • entry of Ca²⁺ also triggers the release of more Ca²⁺ from sarcoplasmic reticulum in the cell (Ca²⁺-induced Ca²⁺ release)
    • outward K⁺ current
      • driven by electrochemical driving force
• Phase 3, repolarization
  • net outward current
    • L-type voltage-gated Ca²⁺ channels close
      • a decrease in inward Ca²⁺ current
    • delayed rectifier K⁺ channels open completely and repolarize the membrane
      • increase in outward K⁺ current
  • inward rectifier K⁺ channels re-open
• Phase 4, resting membrane potential
  • inward and outward currents are equal
  • delayed rectifier K⁺ channels close
  • inward rectifier K⁺ channels are fully open, resetting resting membrane potential at -85 mV