Neuromuscular Junction & Anatomy

Neuromuscular Junction

• A neuromuscular junction connects a motor neuron axon to a skeletal muscle fiber.
• It is a chemical synapse.
• The neuromuscular junction (motor endplate) comprises the terminal part of a motoneuron, the synaptic cleft, and the muscle fiber membrane.

Neuron Anatomy

• Dendrites receive signals.
• Axons transmit signals.
• Nodes of Ranvier facilitate rapid conduction.
• Terminals release neurotransmitters.
• The myelin sheath insulates the axon.
• The neuronal cell body contains the nucleus.
• The nucleus contains the cell's genetic material.

Muscle Fiber Anatomy

• Mitochondria produce energy.
• Myofibrils are the contractile units.
• The sarcolemma is the cell membrane.
• The nucleus contains genetic material.
• T-tubules transmit action potentials.
• Terminal cisternae store calcium.
• Triads consist of a T-tubule and two terminal cisternae.
• The sarcoplasmic reticulum regulates calcium levels.

Chemical Synapse

• Chemical synapses are the predominant type of synapse.
• Neurotransmitters mediate impulse transmission between pre- and postsynaptic neurons.
• An action potential on the presynaptic neuron's axolemma causes neurotransmitter exocytosis.
• Neurotransmitters diffuse across the synaptic cleft and bind to receptors on the subsynaptic membrane.
• This binding leads to a series of changes that generate a postsynaptic action potential.

Motor Unit

• A motor unit includes all muscle fibers innervated by a single motor neuron.

Motor Endplate

• The action potential (AP) arrives at the presynaptic neuron.
• Voltage-gated calcium (Ca2+) channels open, increasing Ca2+ influx.
• Ca2+ triggers the fusion of synaptic vesicles with the presynaptic membrane, releasing neurotransmitters.
• Neurotransmitters bind to ligand-gated channels on the postsynaptic element.
• The ligand-gated channels open, allowing ions to flow and create a postsynaptic potential.
• If the postsynaptic potential reaches threshold, it triggers an action potential.

Acetylcholine (ACh) Synthesis and Storage

• Acetylcholine is synthesized in the axon terminal from acetyl-coenzyme A and choline, catalyzed by cholinacetyltransferase (ChAT).
• It is stored in vesicles with magnesium (Mg2+) and calcium (Ca2+).
• A quantum is the amount of ACh in one vesicle.

Acetylcholine (ACh) Destruction

• ACh is broken down via hydrolysis into choline and acetate by acetylcholinesterase (AChE), choline is then reuptaken.
• ACh can be removed by diffusion.

Acetylcholine (ACh) Secretion

• Exocytosis of ACh involves:
• An action potential (AP)
• An increase in intracellular Ca2+
• Movement of vesicles toward the active zone
• Fusion with the membrane
• ACh diffusion to the receptor

Acetylcholine (ACh) Receptor

• The nicotinic cholinergic receptor (AChR) is a ligand-gated ion channel permeable to sodium (Na+), potassium (K+), and calcium (Ca2+).
• ACh binding to the receptor opens the channel.
• Na+ entry causes depolarization of the motor endplate, known as the endplate potential.
• This depolarization can trigger an action potential (AP) on the muscle fiber.

Neuromuscular Junction Process

• A presynaptic AP occurs.
• Calcium (Ca2+) channels open.
• Intracellular Ca2+ increases.
• Acetylcholine is released.
• Acetylcholine binds to ACh receptors (AChR).
• The endplate potential is generated.
• An action potential is generated on the muscle fiber.
• Acetylcholine degradation via acetylcholinesterase (AChE) occurs.

Disorders of the Neuromuscular Junction

• The synapse lacks both blood-brain and blood-nerve barriers.
• Autoimmune diseases can affect the neuromuscular junction.
• Presynaptic disorders (affecting ACh release) include Lambert-Eaton myasthenic syndrome, which involves antibodies against neuronal calcium channels.
• Postsynaptic disorders (affecting AChR) include myasthenia gravis, which involves antibodies against nicotinic receptors.

Drugs Affecting the Neuromuscular Junction

• Action potential (AP) origin:
  • Blockers of Na+ channels: tetrodotoxin
  • Blockers of K+ channels: 3,4-diaminopyridine
• Ach secretion:
  • Botulotoxin, Mg2+
• AChR:
  • Depolarizing muscle relaxant: suxamethonium
  • Competitive muscle relaxant: curare
• ACh degradation (blockers of AChE):
  • Short-termed: physostigmine, neostigmine
  • Long-termed: organophosphates

Tetrodotoxin

• Tetrodotoxin is a blocker of sodium (Na+) channels.

Botulotoxin

• Botulotoxin is produced by Clostridium botulinum.

Curare

• Curare comes from Strychnos toxifera.