Synapses and Neuromuscular Control & Nervous System Disorders

Synapses: Two Types

• Dendrites and Axon: Key components of synaptic structure.
• Types of Synapses:
  • Electrical Synapses:
  • Electric current passes directly from presynaptic to postsynaptic cell through gap junctions.
  • Chemical Synapses:
  • Electrical signal converted into a chemical signal (neurotransmitter) released from the presynaptic cell to act on receptors on the postsynaptic cell.

Gap Junctions

• Formed by the docking of two hemichannels made from connexin or innexin proteins.

Neurotransmitters

• Types of Neurotransmitters:
  1. Classical:
  • Acetylcholine (ACh)
  • Biogenic Amines:
    • Noradrenaline (norepinephrine)
    • Dopamine
    • Serotonin (5-hydroxytryptamine)
    • Histamine
  • Amino Acids:
    • Glutamate
    • γ-aminobutyric acid (GABA)
    • Glycine
  1. Peptides:
  • Substance P
  • Opioids (endorphins, enkephalins)
  1. Unconventional Transmitters:
  • Gases: Nitric oxide (NO)
  • Purines: Adenosine triphosphate (ATP)
  • Lipids: Cannabinoids
• Naming Neurons: Neurons are named based on their neurotransmitter (e.g., cholinergic neurons secrete ACh).

Neurotransmission Dynamics

• Excitatory Neurotransmitter:
  • Depolarizes the postsynaptic cell, leading to an Excitatory Postsynaptic Potential (EPSP).
  • If EPSP is substantial, it can trigger an action potential.
• Inhibitory Neurotransmitter:
  • Hyperpolarizes the postsynaptic cell, leading to an Inhibitory Postsynaptic Potential (IPSP).
  • Makes action potential generation more challenging by moving the membrane potential away from the threshold.

Neurotransmitter Release - Regulated Exocytosis

1. Action potential arrives at the axon terminal.
2. Depolarization opens voltage-gated Ca²⁺ channels, allowing Ca²⁺ to enter the cell.
3. Calcium influx triggers exocytosis of synaptic vesicle contents into the synaptic cleft.
4. Neurotransmitter binds to receptors on the postsynaptic cell, initiating a response.

Acetylcholine (ACh) Metabolism

• Synthesized from:
  • Precursors: Choline (from plasma) + Acetyl CoA (from glucose metabolism).
• Choline Acetyltransferase: Enzyme that catalyzes the formation of ACh.
• ACh is degraded by acetylcholinesterase, breaking it down into acetic acid and choline.

Receptors for Neurotransmitters

• Ionotropic Receptors:
  • Opening/closing of ion channels; rapid response.
• Metabotropic/G-protein Coupled Receptors:
  • Activate second messenger pathways; slower response.
• A single neurotransmitter can bind both ionotropic and metabotropic receptors.

Acetylcholine Receptors

• Nicotinic ACh Receptor (nAChR):
  • An ionotropic receptor, enhanced by nicotine; allows Na⁺, K⁺, and Ca²⁺ to enter when activated.
• Muscarinic ACh Receptor (mAChR):
  • A metabotropic receptor, influenced by muscarine; affects second messenger systems (e.g., activating or inhibiting adenylate cyclase).

Adrenergic Receptors for Noradrenaline

• Subtypes:
  • α1: Activates phospholipase C.
  • α2: Inhibits adenylate cyclase.
  • β1-β3: Activates adenylate cyclase, raising cAMP levels.

Neurons and Neural Pathways

• Organized into circuits that connect sensory input, processing, and motor output:
  • Somatic motor
  • Autonomic
  • Afferent/sensory pathways

Efferent Somatic Motor Pathway

• Controls skeletal muscle:
  • Motor neurons originate in the CNS; myelinated axons project from spinal cord to muscle.
  • Motor units can innervate multiple muscle fibers.

Anatomy of the Neuromuscular Junction

• Involves a motor neuron synapsing with a muscle fiber.
• An action potential leads to the release of ACh, which then binds to nicotinic receptors.

Differences Between Autonomic and Somatic Nervous Systems

• Autonomic Nervous System:
  • Controls involuntary functions; uses ACh and Noradrenaline; two neurons in series.
• Somatic Nervous System:
  • Controls voluntary actions; primarily uses ACh impacting skeletal muscles.

Disorders of Neuromuscular Transmission

• Myasthenic Disorders: Characterized by muscular weakness and fatigue.
  • Types:
  • Autoimmune (e.g., Myasthenia Gravis, Lambert-Eaton Myasthenic Syndrome).
  • Congenital Syndromes affecting ACh receptors and enzyme function.

Myasthenia Gravis (MG)

• Autoantibodies that block, degrade, or destroy postsynaptic nicotinic ACh receptors, leading to muscle weakness.
• Treatment can involve acetylcholinesterase inhibitors to enhance neurotransmission.

Lambert-Eaton Myasthenic Syndrome (LEMS)

• Autoantibodies attack presynaptic voltage-gated Ca²⁺ channels, decreasing ACh release, primarily affecting upper legs and eye muscles.

Depression and Neurotransmitter Imbalance

• Associated with a significant mood disorder affecting many individuals.
• Characteristics: Alterations in mood, sleep disorders, appetite changes.
• Links: Involvement of monoamines (noradrenaline, dopamine, serotonin) and cholinergic activity.
• Treatment: Medications like tricyclics, SSRIs, and MAO inhibitors aim to normalize neurotransmitter levels.

Learning Outcomes

• Comprehend distinctions between types of synapses.
• Understand ACh precursor synthesis and degradation.
• Compare autonomic and somatic systems as well as neurotransmission disorders.