week 5 Cardiac Cell Action Potential and Antiarrhythmics

Cardiac Cell Action Potential

• The cardiac cell action potential is the electrical activity of the heart muscle cells.
• It involves the movement of ions (Na+, K+, Ca++) across the cell membrane, resulting in depolarization and contraction of the myocardium.
• The action potential has three phases: resting state, depolarization, and repolarization.

Role of Ca, Na, and K in the Action Potential

• Calcium (Ca++):
  • Enters the cell and triggers the release of more Ca++ from the sarcoplasmic reticulum.
  • Binds to Troponin C, inducing a change in tropomyosin shape, exposing the active site between actin and myosin, leading to contraction.
• Sodium (Na+):
  • Moves into the cell during depolarization, causing the cell to depolarize and propagate the impulse.
• Potassium (K+):
  • Moves out of the cell during repolarization, helping the cell return to its resting state.

Electrical-Mechanical Coupling

• The electrical activity of the heart precedes mechanical contraction.
• Pacemaker cells have the property of automaticity, meaning they can initiate electrical activity without neural innervation.

Ion Channels and Electrolytes

• Ions move through specific channels in the cell membrane.
• Voltage-gated channels open and close when the membrane potential reaches a certain value.
• Two major forces drive ion transport: concentration gradients and electrical gradients.
• The concentration of ions across the cell membrane:
  • Na+: higher outside (145 mmol) than inside (15 mmol)
  • K+: higher inside (150 mmol) than outside (5 mmol)
  • Ca++: higher outside (2 mmol) than inside (10^-7 mmol)
  • Cl-: higher outside (120 mmol) than inside (5 mmol)

Phases of the Action Potential

• Resting state: no electrical activity takes place.
• Depolarization: Na+ ions move into the cell, causing depolarization and propagation of an impulse.
• Repolarization: the cell attempts to return to its resting state, involving a complex exchange of Na+, K+, and Ca++ ions.

Pacemaker Cells

• Have no resting phase during phase 4.
• Once repolarized, they begin to slowly spontaneously depolarize during phase 4.
• Na+ ions slowly move into the cell, and once the threshold potential is reached, the cell depolarizes.

Refractory Period

• A normal property of cardiac tissue, during which the cardiac cell cannot depolarize again until it has repolarized.
• Divided into two periods: absolute refractory period (ARP) and relative refractory period (RRP).

Antiarrhythmic Drugs

• Classes:
  • Class I: block fast sodium channels (e.g., procainamide, lignocaine, flecainide).
  • Class II: block β-adrenergic receptors (e.g., β-blockers).
  • Class III: block potassium channels (e.g., sotalol, amiodarone).
  • Class IV: block slow calcium channels (e.g., verapamil, diltiazem).

Class I Agents

• Inhibit fast sodium channels, slowing depolarization and conduction.

Class II Agents (β-blockers)

• Competitively inhibit β-adrenergic receptors, reducing sympathetic tone and automaticity.
• Increase the refractory period of the AV node, interrupting reentry arrhythmias.

Class III Agents

• Block potassium channels, prolonging the action potential duration and refractoriness.
• May precipitate torsades de pointes, especially with low K+, low Mg2+, and bradycardia.

Class IV Agents

• Block slow calcium channels, primarily used for supraventricular tachyarrhythmias.
• Verapamil and diltiazem are commonly used.

Other Antiarrhythmic Agents

• Adenosine: acts on the atrium, SA and AV nodes, increasing the refractory period and decreasing automaticity.
• Digoxin: inhibits the Na+/K+-ATPase pump, increasing intracellular Ca++ and inotropy.