01. Cellular Cardiac Electrophysiology and Vectorcardiography

Cardiac electrical activity originates at the level of single-myocyte transmembrane ion channels and integrates spatially into instantaneous three-dimensional dipole vectors.

1. Cellular Electrophysiology & Action Potential Phases

flowchart LR
    P4a["Phase 4: Resting Potential (-90 mV)<br/>IK1 / If Pacemaker"] --> P0["Phase 0: Rapid Upstroke<br/>INa Influx (+20 mV)"]
    P0 --> P1["Phase 1: Early Repol<br/>Ito Outflow"]
    P1 --> P2["Phase 2: Plateau<br/>ICa,L vs IK Balancing"]
    P2 --> P3["Phase 3: Rapid Repol<br/>IKr, IKs Efflux"]
    P3 --> P4b["Phase 4: Restoration<br/>Na+/K+ ATPase, NCX"]

Action Potential Phase	Dominant Ionic Current	Molecular Channel Subunit	Clinical & Pharmacological Significance
Phase 0 (Rapid Upstroke)	Inward $Na^+$ current ($I_{Na}$)	$Nav1.5$ ($SCN5A$)	Target of Class I antiarrhythmics; blocked in Brugada syndrome and TCA overdose.
Phase 1 (Early Repolarization)	Transient outward $K^+$ current ($I_{to}$)	$Kv4.3$ ($KCND3$)	Creates the prominent action potential "notch" in epicardium, underlying the J wave.
Phase 2 (Plateau Phase)	Inward $Ca^{2+}$ current ($I_{Ca,L}$) balanced by $K^+$ efflux	$Cav1.2$ ($CACNA1C$)	Target of non-dihydropyridine CCBs; determines myocardial contractility and refractoriness.
Phase 3 (Final Repolarization)	Rapid ($I_{Kr}$) and Slow ($I_{Ks}$) delayed rectifier $K^+$ currents	$hERG$ ($KCNH2$), $Kv7.1$ ($KCNQ1$)	Target of Class III antiarrhythmics (Amiodarone, Sotalol); mutated in LQTS 1 and 2.
Phase 4 (Diastolic Depolarization / Resting)	Inward rectifier ($I_{K1}$) in working myocytes; Funny current ($I_f$) in SA node	$Kir2.1$ ($KCNJ2$), $HCN4$	Target of Ivabradine ($I_f$ blocker); establishes resting membrane potential ($-90\text{ mV}$).

2. Vectorcardiography & Spatial Dipole Theory

The Cardiac Dipole: Wavefront of depolarization creates a microscopic charge separation (positive advancing head, negative tail).
Spatial QRS-T Angle: The 3D spatial angle between the mean QRS vector (depolarization) and mean T vector (repolarization).
- Normal Spatial Angle: $<45^\circ$ (depolarization and repolarization vectors are nearly parallel).
- Abnormal Spatial Angle: $>100^\circ$ (powerful independent predictor of sudden cardiac death, ventricular arrhythmogenesis, and all-cause mortality).
Fragmented QRS ($fQRS$):
- Presence of additional spikes ($>2$ notches) within the QRS complex in $\ge 2$ contiguous leads.
- Indicates inhomogeneous ventricular conduction through scarred, ischemic, or fibrotic myocardium.

3. Multimodality Investigations

Signal-Averaged ECG (SAECG): Filters surface recordings to detect high-frequency, low-amplitude Late Potentials (LPs) at the terminal QRS (marker of slow conduction and reentrant ventricular tachycardia substrate).
Cardiac Magnetic Resonance (CMR): Direct correlation of $fQRS$ and late potentials with Late Gadolinium Enhancement (LGE) myocardial fibrosis.