M04.03.03 The Action Potential in Ventricular Cells

The action potential in ventricular cells is a fundamental concept in cardiac physiology. Understanding its phases, ionic currents, and the molecular mechanisms underlying these processes is crucial for medical students. This detailed note will guide you through the intricate dynamics of ventricular action potentials, enhancing your grasp of this vital topic.

Overview of Ventricular Action Potential

The ventricular action potential is a rapid, transient change in membrane potential that enables the heart to contract and pump blood. It consists of five distinct phases: 0, 1, 2, 3, and 4.

Phases of the Ventricular Action Potential

1. Phase 0: Depolarization
   • Description: Rapid influx of Na+ ions through voltage-gated Na+ channels.
   • Membrane Potential: From -90 mV to +20 mV.
   • Key Ion Channels: Fast Na+ channels (Nav1.5).
2. Phase 1: Initial Repolarization
   • Description: Transient outward K+ current.
   • Membrane Potential: Slight decline from peak.
   • Key Ion Channels: Transient outward K+ channels (Ito).
3. Phase 2: Plateau Phase
   • Description: Balance between Ca2+ influx and K+ efflux.
   • Membrane Potential: Sustained near 0 mV.
   • Key Ion Channels: L-type Ca2+ channels (Cav1.2), delayed rectifier K+ channels (IKr, IKs).
4. Phase 3: Repolarization
   • Description: Dominance of K+ efflux over Ca2+ influx.
   • Membrane Potential: Return to resting potential (-90 mV).
   • Key Ion Channels: Delayed rectifier K+ channels (IKr, IKs), inward rectifier K+ channels (IK1).
5. Phase 4: Resting Potential
   • Description: Stable resting membrane potential maintained.
   • Membrane Potential: -90 mV.
   • Key Ion Channels: Inward rectifier K+ channels (IK1).

Ionic Currents and Their Roles

Key Points to Memorize

• Phase 0: Depolarization due to Na+ influx.
• Phase 1: Initial repolarization due to transient K+ efflux.
• Phase 2: Plateau maintained by the balance between Ca2+ influx and K+ efflux.
• Phase 3: Repolarization driven by K+ efflux.
• Phase 4: Resting potential maintained by inward rectifier K+ channels.

Detailed Mechanisms

1. Phase 0: Depolarization
   • Na+ Channels Open: Rapid opening of fast Na+ channels (Nav1.5) allows Na+ to enter the cell.
   • Membrane Potential Shift: From -90 mV to +20 mV in milliseconds.
2. Phase 1: Initial Repolarization
   • Ito Activation: Transient outward K+ channels (Ito) open briefly, causing a slight decrease in membrane potential.
   • Early Repolarization: This phase is very short and quickly transitions to the plateau phase.
3. Phase 2: Plateau Phase
   • Ca2+ Influx: L-type Ca2+ channels (Cav1.2) open, allowing Ca2+ to enter.
   • K+ Efflux: Delayed rectifier K+ channels (IKr, IKs) simultaneously open, balancing the membrane potential near 0 mV.
4. Phase 3: Repolarization
   • Increased K+ Efflux: Delayed rectifier K+ channels (IKr, IKs) dominate, causing repolarization.
   • Closing of Ca2+ Channels: L-type Ca2+ channels close, stopping Ca2+ influx.
5. Phase 4: Resting Potential
   • IK1 Channels: Inward rectifier K+ channels (IK1) maintain the resting membrane potential.
   • Stable State: Ensures readiness for the next action potential.

Clinical Relevance

• Arrhythmias: Abnormalities in action potential phases can lead to arrhythmias.
• Pharmacological Interventions: Drugs targeting specific ion channels can modulate action potentials to treat arrhythmias.
• Genetic Mutations: Mutations in ion channel genes can disrupt action potential dynamics, leading to inherited cardiac disorders.

Bibliography

1. Bers, D. M. (2002). Cardiac Excitation-Contraction Coupling and Cardiac Contractile Force (2nd ed.). Kluwer Academic Publishers.
2. Katz, A. M. (2010). Physiology of the Heart (5th ed.). Lippincott Williams & Wilkins.
3. Guyton, A. C., & Hall, J. E. (2016). Textbook of Medical Physiology (13th ed.). Elsevier Saunders.
4. Nattel, S., & Maguy, A. (2008). Ion Channel Function and Dysfunction in Cardiac Arrhythmia. Physiological Reviews, 88(3), 1129-1152.
5. Hille, B. (2001). Ion Channels of Excitable Membranes (3rd ed.). Sinauer Associates.