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Basic Science
Physiology
12 notes available
1 Last Minute Review 2 Neurotransmitters 3 Nerves & Neuromuscular Junction 4 Physiology of Muscles 5 Ion Channels & Membrane Physiology 6 Neurohistology & Glial Cells 7 CSF & Blood-Brain Barrier 8 Neuroendocrinology 9 Sleep 10 NCS/EMG Basics 11 EEG Basics 12 Evoked Potentials
Basic Science › Physiology

Nerves & Neuromuscular Junction

Nerves & Neuromuscular Junction

What You'll Learn

  • Nerve structure — endoneurium, perineurium, epineurium; Schwann cells (PNS) vs oligodendrocytes (CNS)
  • Fiber classification — Erlanger-Gasser (Aα through C) and Lloyd-Hunt systems; velocity ≈ 6 × diameter
  • Action potential — resting membrane potential, Na⁺/K⁺ channels, refractory periods, saltatory conduction
  • Synaptic transmission — EPSPs vs IPSPs, temporal vs spatial summation
  • NMJ anatomy & physiology — P/Q-type Ca²⁺ channels, SNARE proteins, safety factor
  • NMJ disorders — MG (postsynaptic, decrement), LEMS (presynaptic, increment), Botulism (SNARE cleavage)
  • Nerve injury — Seddon vs Sunderland classification, Wallerian degeneration timeline
  • Channelopathies — hyperkalemic PP (Na⁺ channel, myotonia), hypokalemic PP (Ca²⁺ channel, no myotonia)
HighYield Pearls
  • Conduction velocity ≈ 6 × diameter (µm): Aα 12–22 µm → 70–120 m/s; Aδ 1–5 µm → 5–30 m/s; C 0.4–1.2 µm unmyelinated → 0.5–2 m/s.
  • Fiber-by-function: Aα = Ia/Ib + α-motor; Aβ = II touch/pressure; Aγ = fusimotor to muscle spindle; Aδ = III sharp/fast pain + cold; B = preganglionic autonomic (lightly myelinated); C = IV slow pain/warm + postganglionic autonomic.
  • Saltatory architecture: Nav1.6 at node — Caspr1 + contactin-1 + NF155 at paranode (axoglial junction) — Kv1.1/1.2 at juxtaparanode. Antibodies vs NF155, NF186, Caspr1, contactin-1 = nodopathies (CIDP variant, poorly IVIG-responsive, treat with rituximab).
  • PMP22 dose effect: duplication → CMT1A (uniform demyelination); deletion → HNPP (tomacula, recurrent pressure palsies).
  • PNS vs CNS myelin: 1 Schwann cell = 1 internode (PNS, regenerates); 1 oligodendrocyte = up to 50 internodes (CNS, no regeneration).
  • Presynaptic NMJ cascade: AP → P/Q-type VGCC (LEMS target) → Ca²⁺ → SNARE (synaptobrevin/VAMP + syntaxin + SNAP-25) zippers → ACh release. SV2A = levetiracetam binding site + BoNT-A receptor.
  • Toxin cleavage map: BoNT-A → SNAP-25; BoNT-B/D/F/G → synaptobrevin (VAMP); BoNT-C → syntaxin + SNAP-25; tetanus toxin → synaptobrevin in inhibitory CNS interneurons; α-latrotoxin (black widow) → massive ACh release.
  • Postsynaptic clustering: nerve-derived agrin → LRP4 → MuSK → rapsyn → AChR clusters. Antibodies vs any of these = MG variants.
  • AChR subunit switch: fetal γ → adult ε postnatally. CHRNE mutations → congenital myasthenia.
  • Safety factor: EPP ≫ threshold normally. MG → decrement on 3 Hz RNS. LEMS → ≥60% increment post-exercise / high-frequency RNS (presynaptic facilitation).
  • MEPP vs EPP: MEPP = spontaneous single-vesicle quantum (~0.5 mV); EPP = nerve-evoked sum of ~100–200 quanta.
  • Succinylcholine red flags: CONTRAINDICATED in malignant hyperthermia, hyperkalemia, denervation injury, severe burns, recent SCI — risk of lethal hyperkalemia from up-regulated extrajunctional AChRs.
  • Reversal agents: neostigmine reverses non-depolarizing blockers (roc/vec/atrac/cisatrac); sugammadex encapsulates rocuronium & vecuronium specifically.
  • Congenital myasthenia treatment traps: slow-channel → AVOID pyridostigmine, use fluoxetine/quinidine; DOK7 → AVOID pyridostigmine, use ephedrine/salbutamol; fast-channel + RAPSN + ChAT → AChEI helps.
  • Ice-pack test: cooling inhibits AChE → ptosis improves ≥2 mm in ocular MG (cheap bedside test).
  • Magnesium & NMJ: high Mg²⁺ competes with Ca²⁺ at presynaptic VGCC → reduced ACh release → weakness; avoid IV Mg in MG / eclampsia overlap.
🔍 Quick ReferenceNerve fiber types · NMJ structure · Disease / drug
Nerve fiber types / properties
  • Aα (Ia/Ib) → muscle spindle primary + GTO afferents + α-motor; 12–22 µm, 70–120 m/s
  • Aβ (II) → touch / pressure / vibration; 5–12 µm, 30–70 m/s
  • Aγ → fusimotor to intrafusal muscle spindle fibers (sets spindle gain)
  • Aδ (III) → fast/sharp pain + cold + crude touch; 1–5 µm, 5–30 m/s; first pain
  • B fiber → preganglionic autonomic, lightly myelinated, 3–15 m/s
  • C fiber (IV) → slow/burning pain + warmth + postganglionic autonomic; unmyelinated, 0.5–2 m/s; second pain
  • Velocity rule → v (m/s) ≈ 6 × diameter (µm) for myelinated fibers
  • Saltatory conduction → AP jumps node-to-node at Ranvier nodes (Nav1.6 clustered)
NMJ structure / signaling
  • P/Q-type VGCC (Cav2.1) → presynaptic Ca²⁺ influx; LEMS antibody target
  • SNARE complex → synaptobrevin (VAMP) + syntaxin + SNAP-25 zipper for vesicle fusion
  • SV2A → synaptic vesicle protein; levetiracetam & BoNT-A binding site
  • ChAT → acetylcholine synthesis from choline + acetyl-CoA in nerve terminal
  • Hemicholinium-3 → blocks high-affinity choline reuptake into terminal
  • Vesamicol → blocks VAChT (vesicular ACh transporter) loading
  • Nicotinic AChR (adult) → pentamer 2αβδε (fetal γ → adult ε switch postnatally)
  • α-bungarotoxin → irreversibly binds α-subunit of nicotinic AChR (krait venom)
  • Agrin → LRP4 → MuSK → rapsyn → AChR clustering pathway at end-plate
  • AChE in synaptic cleft → hydrolyzes ACh → choline + acetate; ends signal
  • MEPP → miniature end-plate potential from single spontaneous vesicle (~0.5 mV)
  • EPP → evoked end-plate potential = sum of many quanta; depolarizes > threshold → muscle AP
  • Safety factor → ratio of EPP amplitude to threshold; reduced in MG, normal in LEMS at rest
  • Caspr1 + contactin-1 + NF155 → paranodal axoglial junction (septate-like)
  • Kv1.1 / Kv1.2 → juxtaparanodal K⁺ channels (under the myelin)
  • Nav1.6 → node of Ranvier Na⁺ channel cluster
  • MAG (myelin-associated glycoprotein) → periaxonal myelin; anti-MAG IgM → distal acquired demyelinating symmetric neuropathy
Disease / drug association
  • Decrement on 3 Hz RNS → myasthenia gravis (postsynaptic AChR Ab)
  • ≥60% increment post-exercise / 50 Hz RNS → LEMS (P/Q VGCC Ab; small-cell lung cancer)
  • Ice-pack test improves ptosis ≥2 mm → ocular myasthenia gravis
  • Descending flaccid paralysis + dilated pupils + dry mouth in infant → infant botulism (BoNT cleaves SNAREs)
  • BoNT-A cleaves SNAP-25 → botulinum toxin / therapeutic onabotulinumtoxin
  • BoNT-B cleaves synaptobrevin (VAMP) → rimabotulinumtoxinB
  • Tetanospasmin cleaves synaptobrevin in Renshaw cells → tetanus (loss of glycine/GABA inhibition → spastic paralysis, trismus, opisthotonos)
  • α-latrotoxin / massive ACh release → black widow spider envenomation
  • PMP22 duplication → CMT1A (uniform demyelinating, onion bulbs)
  • PMP22 deletion → HNPP (tomaculous neuropathy, recurrent pressure palsies)
  • Anti-NF155 / Caspr1 / contactin-1 / NF186 → autoimmune nodopathies (IVIG-refractory CIDP variant, rituximab-responsive)
  • Anti-MuSK MG → bulbar/oculobulbar predominant, poor response to AChEI, rituximab effective
  • SLUDGE-M + miosis + fasciculations → cholinergic crisis / organophosphate poisoning (treat atropine + pralidoxime)
  • Succinylcholine in burns / SCI / denervation → lethal hyperkalemia (up-regulated extrajunctional AChR)
  • Sugammadex → specific encapsulating reversal of rocuronium / vecuronium
  • Neostigmine / pyridostigmine → reverse non-depolarizing blockade; first-line symptomatic MG therapy
  • Edrophonium (Tensilon) → short-acting AChEI; historic MG diagnostic test
  • 3,4-diaminopyridine (amifampridine) → K⁺ channel blocker → prolongs presynaptic AP → LEMS therapy
  • Slow-channel CMS → AVOID pyridostigmine; treat with fluoxetine or quinidine
  • DOK7 CMS → AVOID pyridostigmine; treat with ephedrine or salbutamol
  • RAPSN / fast-channel / ChAT CMS → AChEI responsive
  • COLQ CMS (end-plate AChE deficiency) → AVOID AChEI; treat with ephedrine/salbutamol
  • High Mg²⁺ (eclampsia infusion) → blocks presynaptic Ca²⁺ entry → weakness; avoid in MG
  • Aminoglycosides, fluoroquinolones, telithromycin → worsen MG (presynaptic Ca²⁺ + postsynaptic AChR effects)
Nerve Structure

Neuron Components

  • Soma (cell body) — contains nucleus, Nissl substance (rough ER), site of protein synthesis
  • Axon — single process for impulse conduction; axon hillock has lowest threshold for AP generation
  • Dendrites — multiple branching processes; receive synaptic input
  • Axonal transport:
    • Anterograde (soma → terminal): kinesin; fast (200–400 mm/day) for vesicles, slow (1–5 mm/day) for cytoskeletal proteins
    • Retrograde (terminal → soma): dynein; carries growth factors, viruses (rabies, herpes)

Peripheral Nerve Connective Tissue Layers

Layer Surrounds Clinical Significance
Endoneurium Individual nerve fibers Must be intact for accurate regeneration; contributes to blood-nerve barrier
Perineurium Fascicles (fiber bundles) Main component of blood-nerve barrier; provides tensile strength
Epineurium Entire nerve trunk Contains vasa nervorum; target of surgical repair

Myelinating Cells

Feature PNS — Schwann Cells CNS — Oligodendrocytes
Cell-to-axon ratio 1 Schwann cell : 1 internode 1 oligodendrocyte : up to 50 internodes
Regeneration support Good — forms bands of Büngner Poor — inhibitory environment (Nogo, MAG)
Diseases GBS, CIDP, CMT MS, leukodystrophies
Board Pearl

The perineurium is the primary barrier of the blood-nerve barrier. It is the structure that must be breached in perineuritis (e.g., leprosy). Schwann cells myelinate one internode each; oligodendrocytes myelinate up to 50 — explaining why CNS demyelination is more devastating.

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