Depolarization and Repolarization: Cellular Mechanisms
Depolarization is the process by which cardiac myocytes shift from their resting membrane potential (approximately -85 mV) toward a positive voltage through rapid ion channel activation, while repolarization is the return to resting potential through sequential phases that restore the cell's electrical baseline.
Depolarization Process
Normal automaticity results from phase 4 spontaneous depolarization of the transmembrane action potential, arising from a normal resting potential, reaching threshold and initiating an action potential 1. The process involves:
- Resting state: Ventricular myocardial cells maintain a resting transmembrane potential of approximately -85 mV 2
- Threshold activation: When the membrane potential reaches threshold, rapid depolarization occurs
- Ion channel dynamics: Changes in ion channel or transporter function and expression alter the initiation or propagation of the cardiac action potential 1
In pathological states, abnormal automaticity arises from a partially depolarized membrane potential that is usually close to the activation potential for calcium channels. During acute myocardial infarction or transient ischemia, increased extracellular potassium causes partial depolarization of the resting membrane potential, creating injury currents between infarcted/ischemic tissue and healthy myocardium 1.
Repolarization Process
Repolarization occurs in distinct phases, with the ST segment corresponding to the plateau phase (phase 2) and the T wave corresponding to rapid ventricular repolarization (phase 3) 2.
Phase 2 (Plateau Phase - ST Segment)
- The transmembrane voltage changes slowly during this phase and remains at approximately the same level in all ventricular myocardial cells 2
- Under normal conditions, only small voltage gradients are present
- This corresponds to the ST segment on the ECG, which is normally nearly flat and isoelectric 2
Phase 3 (Rapid Repolarization - T Wave)
During phase 3, the transmembrane action potential repolarizes from its plateau voltage of approximately +10 mV to its resting level of approximately -85 mV 2. Key characteristics include:
- Spatial sequence: Repolarization proceeds from epicardium to endocardium, opposite to the direction of ventricular depolarization 2
- Temporal heterogeneity: The action potential duration of epicardial cells is shorter than that of endocardial and midmyocardial cells 2
- Voltage gradients: The interventricular and intraventricular voltage gradients created as cells undergo rapid sequential repolarization generate the T wave on the body surface ECG 2
Clinical Significance
Abnormal Depolarization
In ischemia, abnormal automaticity may occur in both ventricular myocytes and Purkinje fibers, and may enhance normal automaticity in Purkinje fibers in the ischemic zone 1.
Abnormal Repolarization
Primary repolarization abnormalities result from changes in the shape and/or duration of the repolarization phases of the transmembrane action potential occurring in the absence of changes in depolarization 2, 3. These may be caused by:
- Ischemia
- Myocarditis
- Drugs and toxins
- Electrolyte abnormalities (particularly calcium and potassium)
- Abrupt heart rate changes
- Catecholamines and sympathetic stimulation 2
Secondary repolarization abnormalities occur as the direct result of changes in the sequence and/or duration of ventricular depolarization, manifested as changes in QRS shape and/or duration 3. Examples include ST-T changes associated with bundle-branch blocks, ventricular preexcitation, and paced ventricular complexes.
Triggered Activity
Early afterdepolarizations occur during late phase 2 or early phase 3 of the action potential in the setting of action potential prolongation due to increased inward currents or decreased repolarizing potassium currents 1. These are the trigger for torsades de pointes VT associated with QT prolongation.
Delayed afterdepolarizations occur after complete membrane repolarization and develop under conditions of intracellular calcium overload 1. Contributing factors include tachycardia, catecholamines, hypokalemia, digoxin toxicity, cardiac hypertrophy, and heart failure.