Neuroscience Chapter: Presynaptic Nerve Terminal

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Questions and Answers

What is the primary role of G-proteins in neurotransmitter receptor activation?

They bind directly to neurotransmitters.

They act as transducers between receptors and second messengers. (correct)

They directly activate ion channels.

They induce gene transcription in the nucleus.

What is the primary mechanism by which local anesthetics inhibit neuronal conduction of pain signals?

Inhibiting neurotransmitter synthesis

Stimulating calcium influx

Blocking voltage gated sodium channels (correct)

Enhancing neuronal action potentials

What is auto-phosphorylation in the context of kinase receptors?

The initiation of gene transcription by receptors.

The process where a receptor phosphorylates itself and another receptor. (correct)

The phosphorylation of neurotransmitters.

The direct phosphorylation of G-proteins.

Which of the following best describes the action of phospholipase A2 activated by G-proteins?

It influences second messenger pathways. Signup and view all the answers

Which local anesthetic is often used for nasal surgery due to its vasoconstrictive properties?

Cocaine Signup and view all the answers

Which receptors are associated with sympathetic and parasympathetic divisions of the autonomic nervous system?

Adrenergic and muscarinic G-protein coupled receptors. Signup and view all the answers

What is a common unwanted effect of high systemic doses of local anesthetics?

Respiratory blockade Signup and view all the answers

Which type of local anesthetics tends to produce the metabolite PABA, associated with allergic reactions?

Esters Signup and view all the answers

What triggers the dissociation of G-protein subunits during receptor activation?

The binding of GTP to the G-protein. Signup and view all the answers

What is the effect of G-protein coupled receptors on intracellular signaling?

They create a cascade of signaling events. Signup and view all the answers

How does succinylcholine achieve muscle relaxation during general anesthesia?

By functioning as a neuromuscular blocker at nicotinic receptors Signup and view all the answers

What outcome is associated with the activation of the insulin receptor via auto-phosphorylation?

Phosphorylation of glucose transport proteins. Signup and view all the answers

Which of the following amide local anesthetics has a longer duration of action?

Bupivicaine Signup and view all the answers

What is a key difference between the action of acetylcholine and succinylcholine at nicotinic receptors?

Succinylcholine leads to channel desensitization Signup and view all the answers

Which of the following describes G-proteins most accurately?

They connect receptors to intracellular effectors. Signup and view all the answers

What is the effect of high doses of local anesthetics that cross the blood-brain barrier?

Seizures Signup and view all the answers

What role do voltage-gated Ca2+ channels play in neurotransmitter release?

They facilitate the influx of Ca2+ into the presynaptic terminal. Signup and view all the answers

What is the 'active zone' in the context of presynaptic nerve terminals?

The location where synaptic vesicles are docked and can release neurotransmitters. Signup and view all the answers

What happens during exocytosis of synaptic vesicles?

Vesicles fuse with the presynaptic membrane to release neurotransmitters into the synaptic cleft. Signup and view all the answers

What is referred to as a 'quantum' in the context of neurotransmitter release?

The amount of neurotransmitter a single synaptic vesicle contains. Signup and view all the answers

What triggers the fusion of synaptic vesicles with the presynaptic membrane?

Increase in intra-cytoplasmic Ca2+ concentration. Signup and view all the answers

Which statement is true regarding the presence of Na+ and K+ channels in the presynaptic nerve terminal?

Na+ and K+ channels are absent in presynaptic nerve terminals. Signup and view all the answers

How does calcium concentration affect neurotransmission?

Elevated calcium levels enhance vesicle fusion with the presynaptic membrane. Signup and view all the answers

What aspect of synaptic vesicles is affected by certain medications?

The release mechanism of synaptic vesicles. Signup and view all the answers

What is the primary function of acetylcholinesterase in the synapse?

To degrade acetylcholine Signup and view all the answers

Which of the following drugs is classified as an acetylcholinesterase inhibitor approved for dementia?

Rivastigmine Signup and view all the answers

How do acetylcholinesterase inhibitors affect acetylcholine levels in the central nervous system?

They increase the levels of acetylcholine. Signup and view all the answers

What role does acetylcholine play in REM sleep?

It is involved in regulating sleep patterns. Signup and view all the answers

Which psychiatric health issue has been suggested to be influenced by acetylcholine levels?

Autism Signup and view all the answers

What is the initial effect of succinylcholine on muscle activity?

Muscle contraction Signup and view all the answers

Which drug directly acts to prevent calcium release during malignant hyperthermia?

Dantrolene Signup and view all the answers

Which of the following drugs is classified as a non-depolarizing muscle relaxant?

Atracurium Signup and view all the answers

What is a major side effect common to both nicotinic antagonists and succinylcholine?

Respiratory paralysis Signup and view all the answers

In patients with pseudocholinesterase deficiency, succinylcholine can lead to which condition?

Severe apnea Signup and view all the answers

Which of the following is a characteristic of malignant hyperthermia?

Continuous muscle contraction Signup and view all the answers

Which drug potentiates GABA-A channel activity and is used as a spasmolytic?

Carisoprodol Signup and view all the answers

What type of muscle relaxant is vecuronium classified as?

Nicotinic antagonist Signup and view all the answers

Study Notes

Presynaptic Nerve Terminal

Presynaptic vesicles contain proteins that sense Ca²⁺ concentration, hold the vesicle in place for release, and are involved in docking, release, and uptake of the vesicle within the presynaptic nerve terminal.
Voltage-gated Na⁺ and K⁺ channels are present in the axon but not in the presynaptic nerve terminal membrane.
Depolarization of the presynaptic terminal activates voltage-gated Ca²⁺ channels (VGCC) located in the presynaptic terminal membrane.
Ca²⁺ influx raises intra-cytoplasmic Ca²⁺ concentrations.
Many synaptic vesicles are located in the active zone, close to the presynaptic terminal membrane.
Increased Ca²⁺ levels bind to Ca²⁺ sensing proteins on synaptic vesicles in the active zone, triggering fusion with the presynaptic nerve terminal membrane.
This fusion releases neurotransmitter into the synaptic cleft through exocytosis, a rapid process requiring a few hundred microseconds.
A single synaptic vesicle contains a quantum of neurotransmitter molecules.
Fusion of individual vesicles results in quantal release of neurotransmitter.
Medications can alter neurotransmission by influencing Ca²⁺ levels or inhibiting vesicle release.

G-Proteins as Transducers of Receptor Activation

Receptors linked to intracellular proteins and enzymes act through G-proteins.
G-proteins bind GTP.
Receptor activation by a neurotransmitter stimulates GTP binding and dissociation of the G-protein into subunits.
Free subunits affect adenylate cyclases, phospholipase C, Phospholipase A2, various kinases, and indirectly ion channels.
G-protein coupled receptors are found throughout the nervous system, including the autonomic nervous system (ANS).

Kinase Receptors as Transducers of Receptor Activation

Kinase receptors undergo autophosphorylation, leading to a cascade of phosphorylation of intracellular proteins.
The insulin receptor is an example of a kinase receptor.
Insulin binding to the receptor triggers dimerization and autophosphorylation, ultimately leading to glucose uptake and storage.

Local Anesthetics

Local anesthetics block neuronal action potentials by blocking voltage-gated sodium channels, inhibiting neuronal conduction of pain signals.
Local anesthetics are reversible and vary in duration of action.
Common examples include lidocaine, mepivacaine, bupivacaine, tetracaine, benzocaine, procaine (Novocain), and cocaine.
Cocaine also blocks reuptake of catecholamines.
Side effects include:
- High systemic doses can lead to death due to blockade of neurons responsible for respiration and cardiovascular problems.
- Depression of skeletal and smooth muscle contraction.
- Seizures at high doses that cross the blood brain barrier.
- Ester analogs produce PABA, which can cause allergic reactions (Amides do not cause this).

Neuromuscular Blockers

Used during general anesthesia to prevent muscle reflex responses and achieve flaccid paralysis.
Two methods:
- Competitive inhibition of acetylcholine at nicotinic channels (skeletal muscle nicotinic receptor antagonists).
- Depolarization blockade with succinylcholine.
Succinylcholine is an agonist at the nicotinic receptor, causing muscle contraction.
Succinylcholine is not degraded by acetylcholinesterase and persists on nicotinic receptors, inhibiting endogenous acetylcholine interaction and blocking muscle contraction.
This leads to channel desensitization and muscle paralysis.
Succinylcholine initially causes muscle contraction (Phase I) followed by rapid desensitization and flaccid paralysis (Phase II).
Drugs:
- Tubocurarine, atracurium, mivacurium, vecuronium, pancuronium, rocuronium (nicotinic antagonists).
- Succinylcholine (depolarizing block).
Side effects include:
- Ganglionic blockade, causing decreased blood pressure and tachycardia.
- Histamine release.
- Respiratory paralysis.
- Malignant hyperthermia and death at high doses.
- Prolonged muscle relaxation and severe apnea in individuals with pseudocholinesterase deficiency.

Spasmolytics (Muscle Relaxants)

Used to block muscle contraction during surgery and manage malignant hyperthermia.
Malignant hyperthermia is a genetic defect triggered by inhalant anesthesia, leading to excessive calcium release from the sarcoplasmic reticulum, causing muscle contraction, oxygen depletion, and hyperthermia.
Dantrolene (Dantrium) blocks calcium release, preventing malignant hyperthermia, but is hepatotoxic.
Other spasmolytics include:
- Diazepam (Valium).
- Carisoprodol (Soma).
- Baclofen.

Acetylcholinesterase Inhibitors

Acetylcholinesterase degrades acetylcholine in the synapse.
Acetylcholinesterase inhibitors used for dementia include donepezil (Aricept) and rivastigmine (Excelon).
These inhibitors cross the blood brain barrier.
Acetylcholine levels are implicated in autism and REM sleep.

Neurotransmitters and Psychiatric Disorders

The discussed neurotransmitters, while important, are not the only ones involved in the CNS or psychiatric disorders.
These neurotransmitters contribute to the basal level or “tone” of the CNS.
Changes in these neurotransmitters are linked to various psychiatric disorders and are targeted by medications that modulate them.

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Description

Explore the mechanisms involved in the presynaptic nerve terminal, including the role of voltage-gated calcium channels and synaptic vesicles in neurotransmitter release. This quiz covers key processes such as vesicle docking, depolarization, and exocytosis. Test your understanding of how calcium influx influences synaptic transmission.