Chapter: 07 Neuromuscular Junction Structure

               

Neuromuscular Junction Structure diagram

Chapter 06: 🔗👇🏻👇🏻👇🏻👇🏻👇🏻

https://mednotesbyrazaullah.blogspot.com/2026/08/chapter-06-skeletal-muscle-fiber.html

Neuromuscular Junction Structure

The neuromuscular junction (NMJ) is described as the specialized chemical synapse where a large, myelinated motor nerve fiber connects with a skeletal muscle fiber near its midpoint. The terminal end of the axon invaginates into the muscle fiber surface to form the synaptic trough ( synaptic gutter), but remains separated from the muscle membrane by a narrow space called the synaptic cleft.

To dramatically increase surface area, the muscle membrane at the bottom of the trough folds into numerous deep invaginations known as subneural clefts. The nerve terminal contains thousands of membrane-bound vesicles filled with acetylcholine (ACh), along with abundant mitochondria that supply ATP for ACh synthesis. When an action potential reaches the terminal, it triggers calcium influx, causing ACh vesicles to fuse with the presynaptic membrane and release acetylcholine into the cleft. The ACh diffuses across to bind ligand-gated receptors concentrated at the tops of the subneural clefts, initiating the muscle action potential.

  • Skeletal muscle fibers are innervated by myelinated nerve fibers.
  • Nerve fibers branch to stimulate multiple muscle fibers.
  • Each nerve ending forms a neuromuscular junction.
  • The junction occurs near the muscle fiber's midpoint.
  • Motor end plate: Branching nerve terminals invaginated in muscle.
  • Covered by Schwann cells to provide fluid insulation.
  • Synaptic gutter/trough: Invaginated muscle fiber membrane space.
  • Synaptic cleft: Space between terminal and muscle membrane (20–30 nm).
  • Subneural clefts: Folds increasing muscle membrane surface area.
  • Terminals contain mitochondria supplying ATP for acetylcholine synthesis.
  • Acetylcholine: Excitatory transmitter stored in 300,000 synaptic vesicles.
  • Acetylcholinesterase: Enzyme in synaptic space destroying acetylcholine.

Secretion of Acetylcholine

  • Nerve impulse releases about 125 acetylcholine vesicles.
  • Action potential opens voltage-gated calcium channels on the terminal.
  • Calcium ions diffuse into the nerve terminal interior.
  • Calcium draws acetylcholine vesicles to neural dense bars.
  • Vesicles fuse and release acetylcholine via exocytosis.

Acetylcholine Receptors and Ion Channels

  • Receptors are acetylcholine-gated channels near subneural clefts.
  • Two acetylcholine molecules bind to alpha subunits.
  • Binding causes a conformational change that opens channels.
  • Channel diameter (0.65 nm) allows positive ions to pass.
  • Negative charges in the channel mouth repel chloride ions.
  • Positively charged sodium ions flow inward in abundance.
  • Negative resting membrane potential (-80 to -90 mV) attracts sodium.
  • Inward sodium flow creates a local end plate potential.

Destruction of Acetylcholine

  • Acetylcholine persists for only a few milliseconds.
  • Acetylcholinesterase in synaptic space rapidly destroys acetylcholine.
  • Small amounts of acetylcholine diffuse away from space.
  • Rapid removal prevents continuous unwanted muscle re-excitation.

End Plate Potential and Excitation

  • Sodium entry increases local potential by 50 to 75 mV.
  • Potential increase above 20 to 30 mV triggers action potential.
  • Curare: Blocks acetylcholine channels, causing weak potential.
  • Botulinum toxin: Decreases acetylcholine release, causing weak potential.

Acetylcholine Formation and Release

  • Small 40-nanometer vesicles form in the motoneuron Golgi apparatus.
  • Axoplasm transports vesicles from spinal cord to nerve terminals.
  • About 300,000 vesicles collect in a single end plate.
  • Acetylcholine synthesizes in cytosol and stores inside vesicles.
  • Each vesicle holds about 10,000 acetylcholine molecules.
  • Nerve action potential opens voltage-gated calcium channels.
  • Internal calcium increases 100-fold, triggering 10,000-fold vesicle fusion rate.
  • About 125 vesicles rupture per action potential via exocytosis.
  • Acetylcholinesterase splits acetylcholine into acetate and choline.
  • Choline is actively reabsorbed to synthesize new acetylcholine.
  • Clathrin-coated pits form new vesicles within 20 seconds.
  • Recyclable vesicles refill with acetylcholine in a few seconds.

Drugs Affecting Neuromuscular Transmission

  • Acetylcholine-like drugs: Methacholine, carbachol, and nicotine stimulate muscle fibers.
  • These drugs resist cholinesterase, causing persistent depolarization and spasms.
  • Inactivating drugs: Neostigmine, physostigmine, and DFP inactivate acetylcholinesterase.
  • Accumulating acetylcholine causes repetitive muscle stimulation and spasms.
  • Can cause fatal choking via laryngeal spasm.
  • Neostigmine/physostigmine inactivate esterase for several hours.
  • DFP is a lethal nerve gas inactivating esterase for weeks.
  • Blocking drugs: Curariform drugs (e.g., D-tubocurarine) block acetylcholine receptors.

Myasthenia Gravis

  • Autoimmune disease affects 1 in 20,000 people.
  • Antibodies block or destroy postsynaptic acetylcholine receptors.
  • Weak end plate potentials fail to trigger action potentials.
  • Severe cases cause death by respiratory muscle paralysis.
  • Anticholinesterase drugs (e.g., neostigmine) temporarily relieve symptoms.

Muscle Action Potential Characteristics

  • Resting potential: -80 to -90 millivolts in skeletal fibers.
  • Duration: 1 to 5 milliseconds (~5 times longer than nerve).
  • Conduction velocity: 3 to 5 m/sec (1/13 of nerve velocity).

Transverse Tubules and Excitation-Contraction Coupling

  • Surface action potentials cannot penetrate deep into large fibers.
  • Transverse tubules (T tubules) extend completely through the fiber.
  • T tubule action potentials trigger calcium release near myofibrils.
  • Calcium release initiates contraction (excitation-contraction coupling).


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