4 - Neurotransmitters Flashcards
What are the major classes of neurotransmitters? (5 classes)
- acetylcholine
- amino acids
- biogenic amines
- neuropeptides
- gases
What neurotransmitter(s) are in the acetylcholine class?
Acetylcholine
What neurotransmitter(s) are in the amino acid class
- glutamate
- GABA
- glycine
What neurotransmitter(s) are in the biogenic amine class?
- norepinephrine
- dopamine
- serotonin
What neurotransmitter(s) are in the neuropeptide class?
- substance P
- met-enkephalin (an endorphin)
What neurotransmitter(s) are in the gas class?
Nitric oxide
Function (1) and examples of malfunctions (2) of acetylcholine
- enables muscle action, learning, and memory
- undersupply, as Ach-producing neurone deteriorate, marks Alzheimer’s disease
Function (1) and examples of malfunctions (2) of dopamine
- influences movement, learning, attention, and emotion
- excess dopamine receptor activity linked to schizophrenia; starved of dopamine, the brain produced the tremors and decreased mobility of Parkinson’s disease
Function (1) and examples of malfunctions (2) of serotonin
- affects mood, hunger, sleep. and arousal
- undersupply linked to depression; Prozac and some other antidepressant drugs raise serotonin levels
Function (1) and examples of malfunctions (2) of norepinephrine
- helps control alertness and arousal
- undersupply can depress mood
Function (1) and examples of malfunctions (2) of GABA (gamma-aminobutyric acid)
- a major inhibitory neurotransmitter
- undersupply linked to seizures, tremors, and insomnia
Function (1) and examples of malfunctions (2) of glutamate
- a major excitatory neurotransmitter; involved in memory
- oversupply can overstimulate brain, producing migraines or seizures (which is why some people avoid MSG, monosodium glutamate)
What are the two major classes of acetylcholine receptor?
Vertebrates have two major classes of acetylcholine receptor, one that is ligand gated and one that is metabolic
Somatic efferent system pathway(s)
CNS -> ACh (nic) activates skeletal muscle
Sympathetic system pathway(s)
CNS -> ACh (nic) -> NA activates blood vessels
CNS -> ACh (nic) -> ACh (mus) activates sweat glands
CNS -> ACh (nic) activates adrenal medulla
Parasympathetic system pathway(s)
CNS -> ACh (nic) -> ACh (mus) activates salivary glands
What are neuromuscular synapses?
Nerves descending from the spinal column are attached to skeletal muscle and form synapses
What does noradrenaline do?
- activates blood vessels causing dilation
- the contraction of certain blood vessels at the skin surface to limit unnecessary blood vessels at the skin surface (want to direct blood away from skin to the muscles)
How is the gut involved in the sympathetic nervous system?
- constriction of the blood vessels to the gut
- this switches of digestion and opens up blood vessels to the heart
How are the liver and lungs involved in the sympathetic nervous system?
- production and release of glucose from the liver to feed the muscles
- dilation of the bronchioles so we get oxygen entering the lungs
- this is to oxygenate the blood for flight or flight
Function of the nicotinic acetylcholine receptor
Depolarise the post-synaptic muscle membrane upon release of ACh permeable to: Na+ (in) and K+ (out)
Structure of the muscle nAChR (4 points)
- the five receptor subunits form a cluster surrounding a central transmembrane pore, the lining of which is formed by the M2 helical segments of each subunit
- these contain a preponderance of negatively charged amino acids, which makes he pore cation selective
- there are two ACh binding sites in the extracellular portion of the receptor, at the interface between the alpha and the adjoining subunits
- when ACh binds, the kinked alpha-helices either straighten out or swing out of the way, opening the channel pore
What forms the ligand binding site for ACh?
multiple subunits- alpha-delta and alpha-gamma subunits
What is tubocurarine?
- competitive reversible antagonist of ACh at nicotinic receptors on skeletal muscle cells
- used to relax skeletal muscle in surgery
- actions are reversed by increasing ACh concentration by inhibiting the enzyme (acetylcholinesterase) which destroys ACh
- discovered by the indigenous people of South America - used curacine found on tree bark as arrow poison to cause flaccid paralysis in animals
Example of a competitive reversible antagonist of ACh
Tubocurarine
Subunits of GABA(A) receptors
- beta subunit: principal subunit for GABA
- alpha subunits: principal subunit for BZs
- all subunits: 2 cysteines, alpha-alphas apart
The GABA(A) receptor and its associated binding sites (5 points)
- the receptor is pentameric, being composed of 2 alpha, 2 beta, and 1 gamma subunit
- GABA(A) receptors contain recognitions sites for a variety of clinically relevant drugs
- the binding of GABA in 2 GABA binding sites at the interface between alpha and beta subunits open the receptor associated chloride channel
- the benzodiazepine binding site is located at the interface between alpha and gamma-2 subunits
- barbiturates, ethanol, and neurosteroids bind to sites in the membrane - spanning transmembrane regions of the subunits
What structure is the GABA(A) receptor?
The receptor is pentameric, being composed of 2 alpha, 2 beta, and 1 gamma subunit
What sites do GABA(A) receptors contain?
GABA(A) receptors contain recognitions sites for a variety of clinically relevant drugs
What causes the receptor associated chloride channel to open?
The binding of GABA in 2 GABA binding sites at the interface between alpha and beta subunits open the receptor associated chloride channel
Where is the benzodiazepine binding site located?
The benzodiazepine binding site is located at the interface between alpha and gamma-2 subunits
What compounds bind to sites in the membrane?
Barbiturates, ethanol, and neurosteroids bind to sites in the membrane - spanning transmembrane regions of the subunits
Give two examples of ligand gated ion channels and the synaptic potentials
- acetylcholine produces excitatory post synaptic potentials (epsps)
- GABA and glycine produce inhibitory post synaptic potentials (ipsps)
When there is a stimulus, what does acetylcholine production cause?
An action potential on the post synaptic cleft because there is an influx of sodium
When there is a stimulus, what does GABA(A) receptor cause?
- an inhibitory action in the post synaptic cell, in the post synaptic neurons
- basically switches cell activity off
- causes a tranquillising effect
What happens when the GABA binds to the GABA receptor?
The receptor forms a channel in the cell membrane, allowing the passage of negatively charged chloride ions into the cell
- this causes hyper polarisation - as you increase the negative charge, action action potential is reduced, and the system is depressed
- the cell responds by coming inhibited - the opposite of an action potential - any action potentials in the post-synaptic neuron would be blocked
What does the GABA(A) receptor do?
Opens a chloride ion channel causing hyper polarisation and cell inhibition
