Myocardial Action Potential - Cardiovascular

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