Antiarrhythmic drugs act by altering the flux of ions across the membranes of excitable cells in the heart.

Sodium Channel Blockade

• Sodium channels are responsible for the initial rapid (Phase 0) depolarization of atrial, Purkinje, and ventricular cells.

• Sodium channel activation (opening) is voltage-dependent

• The sodium current entering the cell during phase 0 depolarization is very intense, but brief

• Activation (opening) and inactivation (closing) of cardiac sodium channels is very rapid

• Blockade of sodium channels:

  • Slows the rate and amplitude of phase 0 depolarization

  • Reduces cell excitability

  • Reduces conduction velocity

• SA and AV nodal cells have relatively few sodium channels and therefore lack a rapid phase 0 depolarization.

Calcium Channel (L-type) Blockade

• Calcium channels (L-type) are responsible for the prolonged plateau phase (Phase 2) seen in the action potential of atrial, Purkinje, and ventricular cells.

• L-type calcium channel opening is voltage-dependent, but requires a more positive membrane potential than cardiac sodium channels

• The calcium current entering the cell during phase 2 is intense and prolonged

• L-type calcium channels are slow to activate (open) and slow to inactivate (close)

• Blockade of calcium channels reduces the amplitude and length (time) of phase 2 in atrial, Purkinje, and ventricular cells

• In SA and AV nodal cells, calcium entry through L-type channels represents the major ion flux during depolarization.

Potassium Channel Blockade

• Potassium channels, particularly the channel giving rise to the "delayed rectifier current", are activated during the repolarization (Phase 3) of the action potential.

• Blockade of potassium channels prolongs action potential duration.

  • Prolongation of action potential duration usually results in an increase in effective refractory period

Category: Pharmacology Notes