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LF260 Neuropharmacology > Lecture 4: PNS Pharmacology > Flashcards

Lecture 4: PNS Pharmacology Flashcards

1
Q

Describe the organization of the PNS

A
  • Enteric: gut
  • Somatic: skeletal muscle
  • Autonomic: all targets except skeletal
    • Parasympathetic: rest and digest
    • Sympathetic: flight/fight response
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2
Q

What do afferent fibers do?

A

Carry sensory information TO the CNS

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3
Q

What do efferent fibers do?

A

Carry signals from CNS to the periphery

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4
Q

What are the key components of a synaptic junction?

A
  • Presynaptic Terminal: Contains synaptic vesicles with neurotransmitters and mitochondria for energy production. Typically around 40nm in diameter.
  • Synaptic Cleft: The gap between the presynaptic terminal and the postsynaptic density, typically around 20nm wide.
  • Postsynaptic Density: Contains receptors that evolve as neurotransmitters activate, facilitating signal transmission.
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5
Q

The efferent pathways of the ANS consist of 2 neurons. What are they?

A
  • Preganglionic neurons
  • Postganglionic neurons
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6
Q

Preganglionic neurons

A
  • Arise in the brain stem / lateral horn of the spinal cord
  • Synapse w postganglionic neurons
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7
Q

Postganglionic neurons

A

Cell bodies of which are contained within an autonomic ganglion (collection of nerve cell bodies) that lies outside the CNS

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8
Q

Describe the process of synaptic transmission

A
  1. Synthesis: Neurotransmitters are synthesized within the neuron.
  2. Storage: Neurotransmitters are protected from metabolic enzymes in the cytoplasm, packaged into synaptic vesicles at high concentrations, and potentially released in discrete bursts (quanta).
  3. Release: Synaptic vesicles dock at the presynaptic membrane, calcium ions (Ca2+) enter the terminal upon depolarization, leading to vesicle fusion and neurotransmitter release. The vesicle membrane is then recycled.
  4. Activation: Neurotransmitters bind to receptors on the postsynaptic membrane, causing biochemical changes in the target tissue, excitation or inhibition of the tissue, and coupling to signal transduction systems.
  5. Inactivation: Receptors may become desensitized, and neurotransmitters may be metabolized by inactivating enzymes into inactive forms.
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9
Q

What are the main components of the spinal cord in terms of sensory and motor pathways?

A
  • Sensory Pathways:
    • Sensory receptors transmit signals through afferent neurons, which enter the spinal cord via the dorsal horn.
    • Interneurons are interposed between sensory afferents.
  • Motor Pathways:
    • Efferent neurons carry signals from the Central Nervous System (CNS) to the periphery.
    • Efferent neurons exiting the spinal cord’s ventral horn innervate skeletal muscle.
    • Neurons in the lateral horn belong to the Autonomic Nervous System (ANS).
  • Interneurons:
    • Found throughout the spinal cord.
    • They may receive inputs from the brain and are interposed with afferent neurons.
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10
Q

What are the key components of a synapse in the nervous system?

A
  • Presynaptic Terminal:
    • Contains synaptic vesicles filled with neurotransmitters.
    • Typically measures around 40nm in size.
    • Often contains mitochondria to provide energy for neurotransmitter release.
  • Synaptic Cleft:
    • The space between the presynaptic terminal and the postsynaptic density.
    • Measures approximately 20nm.
    • Represents the physical gap between neurons.
  • Postsynaptic Density:
    • Contains receptors that respond to neurotransmitters released from the presynaptic terminal.
    • Neurotransmitter activation occurs in this region, facilitating signal transmission.
    • Neurotransmitters are released from specific regions of the presynaptic terminal known as the active zone.
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11
Q

What are the key features of the somatic nervous system in relation to skeletal muscle innervation?

A
  • Function: Serves skeletal muscle.
  • Axonal Pathway: Axons emerge from the ventral horn of the spinal cord.
  • Axon Length: Length of the axon is dependent on the distance to the muscle, varying with individual height.
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12
Q

Describe the structure of the NMJ

A
  • Nerve fibers extend to form axon branches at the NMJ.
  • One axon may branch into collaterals, which innervate various muscle fibers.
  • The number of muscle fibers innervated varies, with fewer fibers in muscles like the eye muscles and more in muscles like the quadriceps and biceps.
  • Acetylcholine (ACh) is the neurotransmitter used at the neuromuscular junction.
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13
Q

What are varicosities in the context of the autonomic nervous system (ANS)?

A
  • Varicosities are structures along nerve branches in the ANS that contain neurotransmitters.
  • They are labeled with fluorescent dye and are draped over the target tissue, providing multiple points of contact.
  • Varicosities form a nerve ending net, serving as the site of neurotransmitter release onto the target tissue.
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14
Q

What neurotransmitter is released from all parasympathetic postganglionic neurons at the neuroeffector junction?

A

ACh

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15
Q

What neurotransmitter is predominantly released from postganglionic neurons in the sympathetic nervous system (SNS)?

A

Noradrenaline (AKA norepinephrine)

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16
Q

What is the exception regarding neurotransmitter release in the sympathetic nervous system?

A

Sweat glands, which are innervated by sympathetic postganglionic neurons that release acetylcholine (ACh) instead of noradrenaline.

17
Q

What is the role of adrenaline (epinephrine) in the sympathetic nervous system?

A
  • Released from the chromaffin cells of the adrenal medulla in response to stimulation by preganglionic neurons of the sympathetic nervous system.
  • It functions as a hormone when released into the bloodstream, allowing it to reach various tissues and organs throughout the body, even those not directly innervated by the sympathetic nervous system.
18
Q

ACh activates 2 broad classes of receptors

A
  • Nicotinic receptors
  • Muscarinic cholinoceptors
19
Q

What are the two classes of adrenoreceptors?

A
  • Alpha
  • Beta
20
Q

How is transmission described at synapses where the neurotransmitter is noradrenaline?

A

Noradrenergic

21
Q

What receptors are activated by noradrenaline at these synapses?

A

Adrenoreceptors

22
Q

Nictotinic cholinoreceptors (nAChR)

A
  • Ligand-gated ion channels
  • Ionotropic receptors
23
Q

Muscarinic cholinoceptors (mAChR)

A
  • All subtypes of adrenoceptor
  • G-protein coupled receptors-metabotropic receptors
24
Q

What is the structure of the ionotropic receptors involved in neurotransmission?

A

5 subunits, forms donut shape

25
Q

How do ions flow through these receptors?

A

Ions flow through the hole in the center of the “donut” depending on the electrochemical gradient.

26
Q

Where are the binding sites located in these receptors?

A

The binding sites are present in the alpha subunits of these receptors

27
Q

What region forms the pore of the receptor?

A

The N2 region forms the pore, aligning the “hole” of the donut. It contains amino acid residues that determine the activity for a particular ion.

28
Q

What happens when an agonist of the neurotransmitter binds to the receptor?

A

Binding of the agonist induces a conformational change, leading to the opening of the receptor, allowing ions to flow in or out depending on the electrochemical gradient.

29
Q

What is another term for these receptors based on their subunit composition?

A

Pentameric [5 subunits]

30
Q

What are some key features of muscarinic receptors?

A
  • There are five types of muscarinic receptors.
  • Drugs can interact with each receptor slightly differently.
  • Each receptor has a different binding pocket, which allows chemists to design molecules that will interact with only specific receptors.
  • These receptors exhibit additional diversity of signaling.
  • When they bind acetylcholine (Ach), they have different intracellular functions.
31
Q

What are the key neurotransmitters and receptors involved in the somatic and autonomic nervous systems?

A
  • Acetylcholine (ACh) + nicotinic receptors
    • Somatic motor neurons
    • Ganglia of the PNS and SNS
    • Adrenal medulla: acts as a modified ganglia, releases adrenaline
  • Muscarinic receptors
    • Postganglionic neurons in PNS → allow for slower responses compared to nicotinic receptors
    • Sweat glands (exception in SNS)
  • Noradrenaline + αβ receptors
    • Sympathetic nervous system

LF260 Neuropharmacology (14 decks)

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