Cardiac & Vascular Electrophysiology
Sodium spikes, calcium plateaus, and the funny current that keeps you ticking
Two kinds of cardiac action potential
Fast-response cells. Atrial and ventricular myocytes and Purkinje fibers rest near −90 mV and fire a sodium-driven phase 0; the steep upstroke conducts rapidly. Working myocytes have a stable phase 4 and no automaticity, whereas Purkinje fibers show slow diastolic depolarization and serve as latent pacemakers.
Slow-response cells. SA and AV nodal cells have no stable resting potential: phase 4 drifts upward spontaneously (automaticity), and phase 0 is carried by calcium, so the upstroke is gentle and conduction slow.
Potassium sets the baseline. Resting membrane potential reflects the high resting K+ permeability, so changes in serum potassium alter excitability in every cell type. Cells are electrically coupled through gap junctions in the intercalated discs, letting depolarization spread cell to cell.
| Feature | Fast response (myocytes, Purkinje) | Slow response (SA and AV nodes) |
|---|---|---|
| Phase 4 | Stable near −90 mV (IK1) in myocytes; slow diastolic drift in Purkinje (latent pacemaker) | Unstable; funny current (If) plus T-type Ca2+ |
| Phase 0 | Voltage-gated Na+ influx, steep | L-type Ca2+ influx, slow |
| Phases 1 and 2 | Present (Ito notch, Ca2+ plateau) | Absent |
| Conduction | Fast | Slow (AV nodal delay) |
| Main drug handles | Class I Na+ blockers, class III K+ blockers | β-blockers, non-dihydropyridine Ca2+ blockers, ivabradine |
The ventricular myocyte action potential
| Phase | Event | Dominant current |
|---|---|---|
| 0 | Rapid depolarization | Fast voltage-gated Na+ influx |
| 1 | Brief partial repolarization | Na+ channels inactivate; transient outward K+ (Ito) |
| 2 | Plateau | L-type Ca2+ influx balanced by K+ efflux |
| 3 | Rapid repolarization | Delayed-rectifier K+ efflux as Ca2+ channels close |
| 4 | Stable rest near −90 mV | Inward-rectifier K+ (IK1) |
Plateau and contraction. The Ca2+ entering in phase 2 opens ryanodine receptors (RyR2) on the sarcoplasmic reticulum, releasing a much larger Ca2+ store (Ca2+-induced Ca2+ release). Ca2+ binds troponin C and cross-bridges cycle — excitation-contraction coupling. Relaxation follows as SERCA pumps Ca2+ back into the SR and the Na+/Ca2+ exchanger extrudes it.
Potassium disorders. Hyperkalemia partially depolarizes cells and inactivates Na+ channels, slowing conduction (peaked T waves, then a widening QRS). Hypokalemia delays repolarization (flattened T waves, U waves, longer QT) and favors ectopy.
Refractoriness. During the absolute (effective) refractory period, inactivated Na+ channels cannot reopen, so no stimulus can fire a new action potential; during the relative refractory period a stronger-than-normal stimulus can. The long Ca2+ plateau keeps the cell refractory until contraction is nearly over, so cardiac muscle cannot be tetanized — it must relax and refill — and re-entry is discouraged.
Vascular smooth muscle. Vessel tone uses a different Ca2+ switch, which explains why some Ca2+ channel blockers act mainly on arteries.
| Feature | Cardiac myocyte | Vascular smooth muscle |
|---|---|---|
| Ca2+ source | L-type influx triggers SR release (RyR2) | L-type influx on depolarization; IP3-driven SR release after α1 (Gq) stimulation |
| Ca2+ target | Troponin C | Calmodulin → myosin light-chain kinase |
| Relaxation | SERCA reuptake, Na+/Ca2+ exchange | Myosin light-chain phosphatase, activated by NO → cGMP |
| Selective Ca2+ blockers | Verapamil, diltiazem (heart and nodes) | Dihydropyridines such as nifedipine, amlodipine |
Pacemaker cells and the conduction system
The funny current. Nodal phase 4 is a slow spontaneous depolarization driven by If — Na+ influx through HCN (hyperpolarization-activated cyclic nucleotide-gated) channels that open as the cell repolarizes — joined late in phase 4 by T-type Ca2+ current. The slope of phase 4 sets the heart rate.
Ivabradine selectively blocks If, flattening phase 4 and slowing the sinus rate without affecting contractility or blood pressure.
Nodal upstroke. Nodal phase 0 is L-type Ca2+ influx (no fast Na+ channels), so the upstroke is slow, which is why AV nodal conduction is slow. Phase 3 is K+ efflux; phases 1 and 2 are absent.
Pacemaker hierarchy. The fastest pacemaker captures the heart and suppresses the others (overdrive suppression); latent pacemakers take over only if the faster ones fail or are blocked.
Conduction velocity. Fastest to slowest: Purkinje fibers → atrial muscle → ventricular muscle → AV node (mnemonic: Park At Venture AVenue). Rapid Purkinje spread makes ventricular contraction nearly synchronous, while the slow AV node adds a delay of about 0.1 s — the main component of the PR interval — so atrial contraction finishes filling the ventricles before systole.
The ECG and the QT interval
- P waveAtrial depolarization; atrial repolarization is hidden within the QRS.
- PR interval (120–200 ms)AV nodal delay; longer than 200 ms is first-degree AV block.
- QRS (under 120 ms)Ventricular depolarization; widening means slow ventricular spread, as in bundle branch block.
- ST segmentThe plateau (phase 2).
- T waveVentricular repolarization.
QT interval. QT spans ventricular depolarization plus repolarization, i.e., action-potential duration; it shortens as heart rate rises, so it is rate-corrected (QTc). Prolongation predisposes to torsades de pointes, a polymorphic VT with a twisting QRS axis. Causes:
- Congenital potassium-channel mutations: Romano-Ward (autosomal dominant, heart only) and Jervell and Lange-Nielsen (autosomal recessive, with sensorineural deafness)
- Electrolytes: hypokalemia, hypomagnesemia, hypocalcemia
- Drugs: class IA and III antiarrhythmics, macrolides, antipsychotics, and also fluoroquinolones, tricyclic antidepressants, ondansetron, azole antifungals
Torsades de pointes: IV magnesium sulfate is first-line; correct potassium and stop the offending drug.
Autonomic control of rate and conduction
Sympathetic. Norepinephrine on β1 receptors (Gs → ↑ cAMP) increases If and Ca2+ currents, steepening phase 4 to raise the rate (positive chronotropy) and speeding AV conduction (positive dromotropy); in myocytes the same pathway raises contractility.
Parasympathetic. Vagal acetylcholine acts on M2 receptors (Gi → ↓ cAMP), opening ACh-activated K+ channels (IKACh) that hyperpolarize nodal cells while If and Ca2+ currents fall. Phase 4 starts lower and rises more slowly, so the sinus rate and AV conduction slow.
Atropine, a muscarinic antagonist, removes vagal tone to raise heart rate and is used for symptomatic bradycardia. Adenosine uses a similar K+-channel mechanism (A1 receptors) to block the AV node transiently.