Contents · 12 sections
In a nutshell. Action potential (AP) is a rapid, reversible change in membrane potential following the all-or-none law. Neuronal AP phases: resting state (−70 mV, K⁺ leak), local response upon depolarization to threshold (~−55 mV), rapid depolarization (Na⁺ channels, +30 mV), repolarization (K⁺ outward), after-hyperpolarization. Duration is 1–2 ms. Propagation occurs along the axon via sequential depolarization (unmyelinated) or node-to-node (saltatory, myelinated — up to 120 m/s). Clinical aspects: Na⁺ channel blockers (local anesthetics, class IA/IB/IC antiarrhythmics), demyelination (multiple sclerosis), channelopathies.
1. Resting potential
- About −70 mV (neurons), −90 mV (cardiomyocytes), −60 mV (smooth muscle).
- Generated by uneven ion distribution: high intracellular K⁺, high extracellular Na⁺ and Cl⁻.
- Maintained by Na⁺/K⁺-ATPase (3 Na⁺ pumped out, 2 K⁺ in) + K⁺ leak channels.
- Nernst equation for K⁺: E_K ≈ −90 mV; for Na⁺: E_Na ≈ +60 mV.
- Goldman equation accounts for the permeability of all ions.
2. Neuronal AP phases
| Phase | Currents | Duration |
|---|---|---|
| Resting state | K⁺ leak | — |
| Local response | Onset of Na⁺ channel activation | Fractions of a ms |
| Depolarization | Na⁺ influx (fast v-g Na⁺ channels) | 0.5 ms |
| Overshoot | Potential reaches +30 mV | — |
| Repolarization | Na⁺ inactivation + K⁺ efflux | 1 ms |
| Hyperpolarization | K⁺ channels still open | 2–5 ms |
| Return to rest | K⁺ channel closure, Na⁺/K⁺-ATPase | — |
3. Ion channels
- Fast Na⁺ channels: 3 states (closed-activated-inactivated); activation threshold −55 mV; inactivation in ~1 ms.
- Slow L-type Ca²⁺ channels: heart (plateau), smooth muscle; target of blockers (verapamil, diltiazem, amlodipine).
- K⁺ channels: delayed rectifier, fast, calcium-activated (BK, SK).
- HCN (funny) channels — in the sinoatrial node; If current responsible for slow diastolic depolarization.
- Ligand-gated: nAChR, GABA_A, NMDA, AMPA — at synapses.
4. All-or-none law
- If the stimulus reaches threshold, an AP develops with full amplitude.
- If subthreshold, a local graded response occurs, and no AP is triggered.
- AP amplitude is independent of stimulus strength (unlike receptor and synaptic potentials).
- Information coding is achieved via firing frequency (rate coding) and patterns.
5. Refractoriness
- Absolute refractory period — during depolarization and early repolarization; Na⁺ channels are inactivated → no stimulus can trigger a new AP.
- Relative refractory period — after returning to rest, but K⁺ channels are still active → a stronger stimulus is required.
- Limits the maximum AP firing frequency (up to 1000 Hz in some neurons).
- In cardiomyocytes, refractoriness lasts almost the entire AP duration (200+ ms) → tetanus is impossible.
6. Propagation
- Unmyelinated fibers: depolarization of one spot → local currents → depolarization of the adjacent segment. Conduction velocity 0.5–2 m/s.
- Myelinated fibers: AP 'jumps' from one node of Ranvier to the next (saltatory conduction); Na⁺ channels are concentrated at the nodes. Conduction velocity up to 120 m/s.
- Fiber diameter: ↑ diameter → ↑ velocity (Aα 70–120 m/s; Aβ 30–70; Aδ 5–30; C 0.5–2).
- Myelin is formed by Schwann cells (PNS) and oligodendrocytes (CNS).
7. Cardiac AP
- Phase 0 (rapid depolarization): Na⁺ inward (working myocytes) or L-type Ca²⁺ (SA and AV nodes).
- Phase 1 (early repolarization): rapid K⁺ efflux.
- Phase 2 (plateau): balance of Ca²⁺ inward and K⁺ outward — specific to the heart.
- Phase 3 (repolarization): Ca²⁺ channels close, K⁺ continues to efflux.
- Phase 4 (resting): −90 mV in working cardiomyocytes; in pacemakers — slow diastolic depolarization (If, followed by T-type Ca²⁺ channels).
8. Blockers and drugs
- Local anesthetics (lidocaine, bupivacaine) — intracellular Na⁺ channel blockade, acting preferentially on active and inactivated states (use-dependent).
- Vaughan-Williams antiarrhythmics:
- — IA (quinidine) — slows phase 0, prolongs AP.
- — IB (lidocaine, mexiletine) — weak, shortens AP.
- — IC (flecainide, propafenone) — strongly slows, does not change AP.
- — II (β-blockers), III (amiodarone, sotalol — K⁺ blockade), IV (Ca²⁺ blockers).
- Anticonvulsants: carbamazepine, phenytoin, lamotrigine — Na⁺ channel blockade.
- Tetrodotoxin (pufferfish), saxitoxin — Na⁺ channel blockade.
9. Channelopathies
- Long QT syndrome (LQT): mutations in K⁺ channels (KCNQ1, KCNH2/HERG) or Na⁺ channels (SCN5A); risk of torsade de pointes.
- Brugada syndrome: SCN5A — increases the risk of ventricular tachycardia.
- Hyperkalemic periodic paralysis: SCN4A mutation.
- Hypokalemic periodic paralysis: CACNA1S.
- Episodic ataxia type 1: KCNA1.
- Familial hemiplegic migraine: CACNA1A.
- Becker's congenital myotonia: CLCN1.
10. Demyelination
- Multiple sclerosis — autoimmune demyelination in the CNS.
- Guillain-Barré syndrome — acute inflammatory demyelination of the PNS.
- Chronic inflammatory demyelinating polyneuropathy (CIDP).
- Hereditary: Charcot-Marie-Tooth disease (type 1 — demyelinating).
- Effect: AP slowing, conduction block, dispersion → clinical symptoms (paresis, sensory disturbances, visual impairment).
11. Clinical measurements
- EEG — summary electrical activity of the cortex; diagnosis of epilepsy, encephalopathies.
- ECG — summary action potentials of cardiomyocytes.
- ENMG — nerve stimulation + recording of muscle AP; conduction velocity, decrement (myasthenia gravis), amplitude.
- Evoked potentials (visual, auditory, somatosensory) — integrative assessment of afferent pathways.
- Patch-clamp — recording currents through single channels (research method).
12. FAQ
Why is there a plateau in cardiomyocytes?
Due to Ca²⁺ influx via L-type channels, which lasts ~200 ms and balances K⁺ efflux. This provides sufficient time for contraction, refractoriness, and prevents tetanus.
How does lidocaine selectively affect diseased cardiomyocytes?
Use-dependent block: the drug binds preferentially to activated and inactivated Na⁺ channels. With frequent depolarization (tachyarrhythmia) — more binding, stronger effect.
Why is hyperkalemia dangerous?
↑ extracellular K⁺ → resting depolarization → Na⁺ channels inactivated → excitability drops → asystole and fibrillation (at ≥ 7 mmol/L).
How does multiple sclerosis differ from Guillain-Barré syndrome?
MS is a chronic CNS disease (demyelination of oligodendrocytes) with relapses and remissions. GBS is an acute PNS polyneuropathy (Schwann cells), ascending weakness, often post-infectious.
What is a use-dependent block?
The drug has a stronger effect on channels that activate frequently. This ensures selectivity: antiarrhythmics affect tachyarrhythmias more than normal rhythm.
See also: Arrhythmias · Multiple sclerosis · Epilepsy · Guillain-Barré syndrome · Physiology Catalog