Somatic Nervous System and NMJ Quiz

Somatic Nervous System

• The Somatic Nervous System (SNS) consists of a single motor neuron that runs from the Central Nervous System (CNS) to the Neuromuscular Junction (NMJ).
• The cell bodies of somatic motor neurons reside in the ventral (anterior) horn of the spinal cord.
• The axon of each motor neuron divides into many branches, each of which innervates a single muscle fiber.

Neuromuscular Junction

• The NMJ is the synapse between the axon terminal of a somatic motor neuron and the motor end plate of a muscle fiber.
• The synaptic cleft is the physical gap between the motor neuron and the muscle fiber.
• The NMJ uses acetylcholine (ACh) as its neurotransmitter.

Neurotransmission at the NMJ

• When an action potential arrives at the axon terminal, it triggers the opening of voltage-gated calcium channels.
• The influx of calcium ions causes the exocytosis of synaptic vesicles containing ACh.
• ACh diffuses across the synaptic cleft and binds to nicotinic acetylcholine receptors (Nm receptors) on the muscle fiber.
• Nm receptors are ligand-gated ion channels that open when ACh binds, allowing sodium ions to flow into the muscle fiber and depolarize the membrane.
• This depolarization triggers a cascade of events that ultimately leads to muscle contraction.

Acetylcholinesterase (AChE)

• AChE is an enzyme that rapidly hydrolyzes ACh into choline and acetate, terminating the action of ACh at the NMJ.
• AChE is highly concentrated at the postsynaptic end plate of the NMJ and in cholinergic neurons.
• It is also found in other tissues, including red blood cells.

Butyrylcholinesterase (BChE)

• BChE is another cholinesterase enzyme with a lower specificity for ACh.
• BChE is primarily synthesized in the liver and is mostly found in plasma and the liver.
• It is also found in glia and many other tissues but is virtually absent in neuronal elements of the central and peripheral nervous systems.
• BChE hydrolyzes ACh at a much slower rate than AChE.

Myasthenia Gravis

• Myasthenia gravis is an autoimmune disease that affects the NMJ.
• The body produces antibodies against the α1 subunits of the Nm receptor-channel complex, leading to a reduction in the number of functional Nm receptors at the NMJ.
• This reduction in Nm receptors results in weakening of skeletal muscles, leading to symptoms such as ptosis, diplopia, and difficulty speaking and swallowing.
• Myasthenia gravis can be managed with AChE inhibitors that increase the effectiveness and duration of ACh binding to the remaining Nm receptors.

The Nicotinic Acetylcholine Receptor (Nm Receptor)

• Nm receptors are ligand-gated ion channels that are activated by ACh.
• They are composed of five protein subunits, arranged in a circular structure.
• ACh binds to two specific sites on the receptor, which triggers a conformational change that opens the channel.
• The opening of the channel allows sodium ions to flow into the muscle fiber, depolarizing the membrane and leading to muscle contraction.
• Nicotinic receptors at autonomic ganglia and in the brain have a different subunit composition.

Somatic Nervous System

• Consists of a single motor neuron running from CNS directly to neuromuscular junction (NMJ).
• Cell bodies of motor neurons are located in the ventral (anterior) horn of the spinal cord.
• Axon divides into multiple branches, each innervating a single muscle fiber.

Neuromuscular Junction (NMJ)

• The synapse between a motor neuron and a muscle fiber.
• Contains a physical gap termed the synaptic cleft.
• Acetylcholine (ACh) is the neurotransmitter responsible for muscle contraction.

Neurotransmission at the NMJ

• Action potential reaches the nerve terminal, leading to Ca²⁺ influx through voltage-gated Ca²⁺ channels.
• Calcium influx triggers exocytosis of vesicles containing ACh into the synaptic cleft.
• ACh diffuses across the synaptic cleft and binds to nicotinic muscle-type receptors (Nm receptors) on the muscle fiber.

Nm Receptors

• Ligand-gated ion channels that increase sodium (Na⁺) influx into the muscle fiber.
• Activation of Nm receptors initiates muscle contraction.

Acetylcholinesterase (AChE)

• Enzyme responsible for rapidly hydrolyzing ACh into choline and acetate.
• Terminates the action of ACh at the NMJ.
• Found in cholinergic neurons and highly concentrated at the postsynaptic end plate of the NMJ.

Butyrylcholinesterase (BChE)

• Another cholinesterase enzyme with lower specificity for ACh.
• Primarily synthesized in the liver and found in plasma, liver, and some other tissues.
• Hydrolyzes ACh at a much slower rate than AChE.

Myasthenia Gravis

• Autoimmune disease affecting Nm receptors at the NMJ.
• Antibodies attack the α1 subunit of the Nm receptor-channel complex.
• Antibodies reduce Nm receptor function by:
  • Cross-linking receptors, leading to internalization and degradation.
  • Causing lysis of the postsynaptic membrane.
  • Directly binding to the receptor and inhibiting its function.
• Results in progressive muscle weakness, often leading to:
  • Ptosis (drooping eyelid)
  • Diplopia (double vision)
  • Difficulty speaking and swallowing
  • Limb weakness
• Severe cases can affect muscles required for respiration.
• Treated with AChE inhibitors to increase the effectiveness and duration of ACh binding to remaining receptors.

Somatic Nervous System

• Consists of a single motor neuron which runs from the CNS to the NMJ.
• Neuron cell body is located in the ventral horn of the spinal cord.
• The neuron axon divides into many branches to innervate individual muscle fibers.

Neuromuscular Junction (NMJ)

• The synapse or synaptic cleft is the physical gap between the somatic motor neuron axon and Nm receptors on skeletal muscle.

Neurotransmission

• Nerve impulse arrival at terminal causes Ca²⁺ influx via voltage-gated channels.
• This influx triggers exocytosis of ACh vesicles into the synaptic cleft.
• ACh diffuses across the cleft and binds to Nm receptors on skeletal muscle.
• Receptor activation causes increase in Na+ influx and initiates muscle contraction.

Nicotinic Muscle Receptors

• Ligand-gated ion channels.
• Composed of α, β, δ, and ε subunits, with acetylcholine binding sites formed at interfaces of the α and δ/ε subunits.
• Acetylcholine binding initiates Na+ influx, membrane depolarization, calcium release from the sarcoplasmic reticulum, and muscle contraction.

Acetylcholinesterase (AChE)

• Enzyme responsible for rapid hydrolysis of acetylcholine (ACh) into choline and acetate.
• Has a fast acting mechanism, hydrolyzing Ach in under a millisecond.
• Highly concentrated at the postsynaptic end plate of the NMJ.

Butyrylcholinesterase (BChE)

• Also known as pseudocholinesterase.
• Primarily synthesized in the liver.
• Hydrolyzes ACh at a slower rate than AChE.

Myasthenia Gravis

• Autoimmune disease affecting Nm receptors at the NMJ.
• Antibodies target the α1 subunit of the Nm receptor-channel complex.
• Leads to reduction in Nm receptor function by:
  • Cross-linking receptors, stimulating internalisation and degradation.
  • Causing lysis of the postsynaptic membrane.
  • Binding to the receptor and inhibiting its function.

Symptoms of Myasthenia Gravis

• Progressive skeletal muscle weakness.
• Ptosis (drooping upper eyelid), diplopia (double vision), difficulty speaking and swallowing, and extremity weakness.

Myasthenia Gravis Management

• AChE inhibitors increase ACh effectiveness and duration at remaining receptors.

Test your understanding of the Somatic Nervous System (SNS) and the Neuromuscular Junction (NMJ). This quiz covers the structure and function of the SNS, as well as the neurotransmission processes at the NMJ. Dive into the details of synapses and motor neuron functions to assess your knowledge.