22-11-21 - Neurotransmitters Flashcards
Learning outcomes
- Define the characteristics of a neurotransmitter, including the main methods of inactivation and explain how the variety of receptors gives scope to the neurotransmitter function.
- Recall the normal major functions of the key neurotransmitters within the major classes.
- Illustrate that abnormalities of specific neurotransmitter systems can cause specific diseases by the use of named examples.
- Provide examples of how synthetic drugs can exert a therapeutic outcome by modifying synaptic transmission in the nervous system.
Describe the 6 steps of signal transduction in the synapse
1) Action potential is sent down the axon of a neuron towards the synapse in the nerve terminal
2) Voltage gated Ca2+ channels open
3) Ca2+ influx causes neurotransmitter-filled vesicles to fuse with the cell membrane
4) The neurotransmitter is released into the synaptic cleft via exocytosis
5) The neurotransmitters bind to post-synaptic receptors, causing the ion channels to open, which results in an ion influx into the post-synaptic neuron
6) Depending on which ion flows in (Na+ or Cl-) the membrane potential of the post-synaptic neuron will move closer or further from the threshold potential
What are the four criteria of neurotransmitters?
• 4 criteria of neurotransmitters:
1) Synthesis
• The NT must be made in the pre-synaptic membrane
2) Storage
• The NT must be stored pre-synaptically
• The exception is Nitrous Oxide in vesicles
3) Release
• The NT must be released on demand
4) Inactivation
• The NT must be inactivated
Describe the 9 steps in the synthesis and action of NT during signal transduction.
What are the 4 potential fates of NT after this?
1) Uptake of precursors
2) Synthesis of NT
3) Uptake/transport of NT into vesicles
4) Degradation of excess NT
5) Depolarisation by action potential
6) Influx of Ca2+ caused by action potential
7) Release of NT by exocytosis
8) Diffusion to postsynaptic membrane
9) Interaction with postsynaptic receptors
• Potential fates of NT after this:
1) Inactivation of NT
2) Reuptake of NT or degraded products by nerve terminal
3) Reuptake and release of NT by non-neuronal cells
4) Interaction with presynaptic receptors
What are the 3 main classification of neurotransmitters?
What are 3 other notable neurotransmitters?
1) Amino acids
2) Biogenic amines – catecholamines or indolamines
3) Peptides
• Other notable neurotransmitter:
1) Acetylcholine
2) Purines (e.g ATP or ADP)
3) Histamine
What are the 3 main amino acid neurotransmitters?
What are they responsible for?
• 3 main amino acid neurotransmitters:
1) Glutamate
• Primary excitatory NT in CNS
• Involved in memory, learning and cell death
2) Gamma-aminobutyric acid (GABA)
• Prinicpal inhibitory in the CNS
• Acts via chloride channels
3) Glycine
• Second most common inhibitory NT in the CNS
• Primary inhibitor NT in the spinal cord and brainstem
What are the most common receptors for Glutamate?
What are 3 examples of this?
How is glutamate inactivated?
What are the 2 neurons glutamate is found in?
• Glutamates action post-synaptically is mostly via ionotropic receptors
• Examples:
1) NMDA receptors – calcium ions
2) Katinate receptors – sodium and potassium ions
3) AMPA receptors – permeable to cations e.g calcium, sodium, potassium
- Glutamate activation occurs by reuptake and recycling to either glutamate or GABA
- Glutamate distribution is widespread within the CNS:
1) Neurons spanning hemispheres (intra and interhemispheric connections)
2) Neurons descending to the brainstem (corticobulbar tracts) or spinal cord (corticospinal tracts)
What can dysfunctions of glutamate cause?
What are 2 ways these seizures can be treated?
- Dysfunction of glutamate can cause epilepsy
- Excess excitation causes a feedback loop
- Can begin as partial seizures
- If become more uncontrolled, can become grand mal seizures
• These seizures can be treated with:
1) Phenytoin
• Increases the refractory period between firings in voltage gated sodium channels
2) Benzodiazepines
• Increases the action of GABA, as it inhibits NT
Where do benzodiazepines bind on the GABAA receptor?
How does this affect GABA?
- Benzodiazepines act on a separate receptor binding site on the GABAa receptor subtype than GABA
- This site controls the ability of GABA to open the Cl- channel
- When benzodiazepines are bound, GABA can open the channel more often
- Benzodiazepines therefore only enhance the actions of existing GABA molecules
What is the role of GABA? Where it found?
What channels does it act on?
How is it inactivated?
How does alcoholism affect GABA?
What does withdrawal cause?
How can this be treated?
- GABA is the principle inhibitory NT in the CNS
- It is found predominantly in the interneurons of the CNS
- It is also found in the striatum and globus pallidus (modules descending motor information)
- It acts as a ligand on gated chloride channels
- GABA is inactivated by presynaptic reuptake
- Alcoholism causes a change in GABA transmission
- Withdrawal results in convulsive movements and seizures
- Can be treated with benzodiazepines
What is the role of glycine?
How is tetanus caused?
What does it cause?
- Glycine is the second most common inhibitory NT in the CNS, but is the primary inhibitory NT in the spinal cord and brainstem
- Tetanus is caused by the toxin from clostridium tetani
- It inhibits the release of glycine, which shifts the excitation-inhibition balance
- Mild effects restricted to muscles innervated by cranial nerves
- More serious effects include epileptiform fits
- Treated with anti-toxin and benzodiazepines
What are the 3 Biogenic amine neurotransmitters that are catecholamines?
Where are they synthesised?
How are they inactivated?
• Biogenic amine neurotransmitters:
1) Dopamine
• Neurotransmitter and neuromodulator
• Involved with pleasure, addiction and movement
2) Noradrenaline (aka norepinephrine)
• Sympathetic neurotransmitter (fight or flight)
• Decrease potentially associated in Parkinson’s and ADHD
3) Adrenaline (aka epinephrine)
• Sympathetic neurotransmitter (fight or flight)
• Peripheral hormone from adrenal medulla
- All of these are synthesised in the bouton
- They are all inactivated principally by re-uptake
What can depleted dopamine cause?
What can overproduction of dopamine cause?
- Parkinson’s
- Tremor, muscle rigidity and bradykinesia r akinesia due to depleted dopamine in the motor co-ordination circuits
- Schizophrenia
- Overproduction of dopamine in the mesolimbic system, treatment is with antipsychotics
What can addiction be developed to?
How does addiction work?
- Addiction can be developed to drugs of abuse, exercise, and certain behaviours, such as sexual activity
- Addiction works through the pleasure centres of the CNS located in the mesolimbic dopamine system
What as an example of biogenic amine that is an indolamine?
What is depression and OCD associated with?
How can this be treated?
What is a receptor agonist?
What are 3 examples of serotonin receptor agonists?
What are major effects of MDMA?
- An example of a biogenic amine that is an indolamine is serotonin
- Depression and OCD are associate with serotonin dysfunction (reduction)
- This can be treated with fluoxetine (Prozac), which is a serotonin re-uptake inhibitor
- A receptor agonist is a chemical that binds to a receptor and activates it to produce a biological response
• Serotonin receptor agonists include:
1) LSD
2) Psilocybin
3) Mescaline
• Major effects of MDMA (ecstasy) is by causing the release and preventing subsequent re-uptake of serotonin
Where are peptide neurotransmitters made?
What are they generally?
What are 3 examples of peptide neurotransmitters?
How do these affect pain and emotional perception of pain?
• Peptide neurotransmitters are made in the cell body and transported to the bouton
• Peptides are generally neurotransmitters or neuromodulators
• Peptide neurotransmitters:
1) Encephalin
2) Endorphin
3) Dynorphin
- Endorphins and encephalins aid in the downregulation of pain by acting on opioid receptors as endogenous ligands
- They also contribute to the emotional perception of pain
What is an example of an ester that is a neurotransmitter?
Where can acetylcholine be found?
What is Alzheimer’s disease associated with?
Where does nicotine act on?
What do anticholinesterases do?
What are its 2 uses?
- Acetylcholine is an example of an ester that is a neurotransmitter
- Acetylcholine can be found in the PNS and CNS
- It is the NT at the neuromuscular junction
- Alzheimer’s disease is associated with dysfunction (reduction) of Ach in the CNS
- Nicotine acts n the nicotinic acetylcholine receptors found in the CNS and PNS
- Anticholinesterases prevent the breakdown of Ach, which prolongs its activity
- It can be used therapeutically (donepezil in Alzheimer’s), but also toxic (insecticides and nerve gas)
