Lecture 4: PNS Pharmacology Flashcards
Describe the organization of the PNS
- Enteric: gut
- Somatic: skeletal muscle
- Autonomic: all targets except skeletal
- Parasympathetic: rest and digest
- Sympathetic: flight/fight response
What do afferent fibers do?
Carry sensory information TO the CNS
What do efferent fibers do?
Carry signals from CNS to the periphery
What are the key components of a synaptic junction?
- 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.
The efferent pathways of the ANS consist of 2 neurons. What are they?
- Preganglionic neurons
- Postganglionic neurons
Preganglionic neurons
- Arise in the brain stem / lateral horn of the spinal cord
- Synapse w postganglionic neurons
Postganglionic neurons
Cell bodies of which are contained within an autonomic ganglion (collection of nerve cell bodies) that lies outside the CNS
Describe the process of synaptic transmission
- Synthesis: Neurotransmitters are synthesized within the neuron.
- Storage: Neurotransmitters are protected from metabolic enzymes in the cytoplasm, packaged into synaptic vesicles at high concentrations, and potentially released in discrete bursts (quanta).
- 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.
- 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.
- Inactivation: Receptors may become desensitized, and neurotransmitters may be metabolized by inactivating enzymes into inactive forms.
What are the main components of the spinal cord in terms of sensory and motor pathways?
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Sensory Pathways:
- Sensory receptors transmit signals through afferent neurons, which enter the spinal cord via the dorsal horn.
- Interneurons are interposed between sensory afferents.
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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).
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Interneurons:
- Found throughout the spinal cord.
- They may receive inputs from the brain and are interposed with afferent neurons.
What are the key components of a synapse in the nervous system?
-
Presynaptic Terminal:
- Contains synaptic vesicles filled with neurotransmitters.
- Typically measures around 40nm in size.
- Often contains mitochondria to provide energy for neurotransmitter release.
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Synaptic Cleft:
- The space between the presynaptic terminal and the postsynaptic density.
- Measures approximately 20nm.
- Represents the physical gap between neurons.
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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.
What are the key features of the somatic nervous system in relation to skeletal muscle innervation?
- 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.
Describe the structure of the NMJ
- 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.
What are varicosities in the context of the autonomic nervous system (ANS)?
- 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.
What neurotransmitter is released from all parasympathetic postganglionic neurons at the neuroeffector junction?
ACh
What neurotransmitter is predominantly released from postganglionic neurons in the sympathetic nervous system (SNS)?
Noradrenaline (AKA norepinephrine)
What is the exception regarding neurotransmitter release in the sympathetic nervous system?
Sweat glands, which are innervated by sympathetic postganglionic neurons that release acetylcholine (ACh) instead of noradrenaline.
What is the role of adrenaline (epinephrine) in the sympathetic nervous system?
- 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.
ACh activates 2 broad classes of receptors
- Nicotinic receptors
- Muscarinic cholinoceptors
What are the two classes of adrenoreceptors?
- Alpha
- Beta
How is transmission described at synapses where the neurotransmitter is noradrenaline?
Noradrenergic
What receptors are activated by noradrenaline at these synapses?
Adrenoreceptors
Nictotinic cholinoreceptors (nAChR)
- Ligand-gated ion channels
- Ionotropic receptors
Muscarinic cholinoceptors (mAChR)
- All subtypes of adrenoceptor
- G-protein coupled receptors-metabotropic receptors
What is the structure of the ionotropic receptors involved in neurotransmission?
5 subunits, forms donut shape
How do ions flow through these receptors?
Ions flow through the hole in the center of the “donut” depending on the electrochemical gradient.
Where are the binding sites located in these receptors?
The binding sites are present in the alpha subunits of these receptors
What region forms the pore of the receptor?
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.
What happens when an agonist of the neurotransmitter binds to the receptor?
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.
What is another term for these receptors based on their subunit composition?
Pentameric [5 subunits]
What are some key features of muscarinic receptors?
- 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.
What are the key neurotransmitters and receptors involved in the somatic and autonomic nervous systems?
- 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
