Cardiac Electrophysiology: The Action Potential
Concept Name
Cardiac Action Potential
Genetic Loci
SCN5A (3p22.2) encodes Nav1.5 sodium channel – mutations cause long QT syndrome type 3 and Brugada syndrome. KCNQ1 (11p15.5) encodes Kv7.1 – mutations cause long QT type 1.
Intracellular Cascade
Phase 0: rapid Na⁺ influx (INa). Phase 1: transient K⁺ efflux (Ito). Phase 2 (plateau): Ca²⁺ influx (L‑type) balanced by K⁺ efflux (IKr, IKs). Phase 3: repolarization via K⁺ efflux. Phase 4: resting potential maintained by Na⁺/K⁺‑ATPase.
Required Cofactors
Mg²⁺ is a cofactor for Na⁺/K⁺‑ATPase. Ca²⁺ is essential for cardiac contraction (excitation‑contraction coupling).
Histology Stains
Desmosomal proteins (desmoplakin, plakoglobin) highlight intercalated discs on immunohistochemistry. Masson’s trichrome distinguishes cardiomyocytes (red) from fibrosis (blue).
EM Findings
Cardiac myocytes show abundant mitochondria (25‑35% of cell volume), organized sarcomeres, and intercalated discs with gap junctions (connexin 43) for electrical coupling.
Knockout Phenotype
Knockout of SCN5A in mice is embryonic lethal at E10‑11 with cardiac developmental defects. Cardiomyocyte‑specific knockout of Cx43 (GJA1) causes ventricular conduction slowing and arrhythmias.
Specific Toxins
Ouabain and digoxin inhibit Na⁺/K⁺‑ATPase, leading to increased intracellular Na⁺ and Ca²⁺. Verapamil blocks L‑type Ca²⁺ channels. Sotalol blocks IKr (hERG channel).