Neurotransmitters Flashcards
1
Q
Discovery of neurotransmitters
A
- Otto Loewi’s experiment showed that cells use chemical transmission
- By electrically stimulating the vagus nerve, Loewi made a dissected frog heart beat slower
- Then, Loewi took a sample of the fluid around the first heart and applied it to the second heart
- This caused the second heart to beat slower ⇒Chemical released by the vagus nerve was controlling the heart rate
- We now know this is the neurotransmitter acetylcholine
- Electrical signals (action potentials) trigger a chemical signal (release of neurotransmitter from synapses)
2
Q
What defines a neurotransmitter
A
- It’s synthesised and stored in the presynaptic neuron
- It’s released by the presynaptic axon terminal upon stimulation
- When experimentally applied, must produce a response in the postsynaptic cell that mimics the response produced by the release of neurotransmitter by the presynaptic neuron
- There must be some retrieval mechanism to remove it from the site of action
3
Q
Neurotransmitter classification
A
- By structure e.g. biogenic amines, amino acids etc
- By function i.e. excitatory vs inhibitory
- By receptor (that it binds to) subtype i.e. ionotropic or metabotropic
4
Q
Neurotransmitter lifecycle
A
- Uptake of precursors + synthesis
- Storage
- Release
- Receptor interaction
- Inactivation
5
Q
Storage of neurotransmitters
A
- Small molecule transmitter
- Synthesised at terminals; packaged in small synaptic vesicles
- Peptide transmitter
- Synthesised at endoplasmic reticulum and transported to the the synapse; packaged in large dense-core vesicles
6
Q
Release of neurotransmitters
A
Exocytosis = fusion of the vesicle membrane with the presynaptic membrane
7
Q
Categories of neurotransmitters
A
- Small molecule (i.e. not proteins) e.g. acetylcholine
- Biogenic amines
- Catecholamines e.g. dopamine, norepinephrine, epinephrine
- Serotonine
- Amino acids: single molecule, building blocks of protein
- Glutamate (excitatory)
- GABA (inhibitory)
- Neuropeptides - lower in concentration, in more specific places. Big molecules, small proteins
- Substance P
- Endorphines
- Enkephalins
- Dynorphins
8
Q
Agonist
A
A chemical that binds to and activates a receptor
9
Q
Antagonist
A
A chemical that binds to and blocks a receptor
10
Q
Ionotropic receptors
A
- Ionotropic receptors can directly “open” or “close” an ion channel
- When neurotransmitter binds to the receptor, the receptor changes conformation, creating an opening for ions to travel through.
- Fast synaptic transmission
- Local and short-term effects
11
Q
Metabotropic receptors
A
- Metabotropic receptors do not have ion channels. Neurotransmitter binds to a G protein-linked receptor and acts through an intracellular second messenger
- In some cases, the secondary messenger will bind to and open ion channels located elsewhere on the membrane
- In other cases, the secondary messenger will trigger a series of enzymatic reactions (Second-messenger cascade)
- This can alter postsynaptic metabolism and indirectly cause ion channels to open
- Indirect action
- Promotes long-lasting effects (typically 100s of ms, but sometimes several hours)
12
Q
Excitatory vs inhibitory postsynaptic potentials
A
- Resulting Postsynaptic Potentials are called excitatory (or EPSPs) if they increase the likelihood of a postsynaptic action potential occurring, and inhibitory (or IPSPs) if they decrease this likelihood.
- Whether a postsynaptic response is an EPSP or an IPSP depends on the type of channel that is coupled to the receptor.
- If Na+ influx occurs the membrane will depolarize (EPSP)
- If Cl- influx occurs the membrane will hyperpolarize (IPSP)
- Determined by receptor type on postsynaptic neuron, not neurotransmitter itself.
13
Q
Acetylcholine
A
- Small molecule neurotransmitter
- Present at many sites within the brain and body, including the neuromuscular junctions
- Two receptor types:
- Nicotinic receptors (ionotropic)
- Muscarinic receptors (metabotropic)
- Excitatory: allows sodium (Na+) to enter the cell
- Function: key role in learning and memory (implicated in Alzheimer’s disease)
- Treatments are acetylcholinesterase (=enzyme that breaks down acetylcholine and removes it from the synaptic cleft) inhibitors: these increase Acetylcholine levels in the brain
14
Q
Catecholamines
A
- Dopamine, norepinephrine, epinephrine
- All synthesised through the same pathway
- Precursor: Tyrosine (essential amino acid)
- Regulation of movement, mood, attention and visceral function
15
Q
Norepinephrine (noradrenaline)
A
- Norepinephrine (noradrenaline)
- Involved in the “fight or flight response”:
- Mobilizes the brain and body for action by activating the sympathetic nervous system
- It increases heart rate, blood flow to skeletal muscle, triggers the release of glucose from energy stores
- Levels are lowest during sleep, rises during wakefulness, and reaches much higher levels during situations of stress or danger
- Increases arousal and alertness, promotes vigilance, enhances formation and retrieval of memory, and focuses attention; it also increases restlessness and anxiety.
16
Q
Dopaminergic systems
A
- Mesolimbic pathway: ventral tegmental area (VTA) of the midbrain to the ventral striatum → reward/reinforcement learning
- Mesocortical pathway: VTA to prefrontal cortex→ planning/short term memory
- Nigrostriatal pathway: substantia nigra of the midbrain to the dorsal striatum → motor functions, Parkinson’s disease (degeneration of substantia nigra)
17
Q
Serotonin
A
- Precursor: Tryptophan, an essential amino acid found in grains, meat, dairy products and chocolate
- Serotonergic neurons are found in the raphe nuclei of the pons and upper brainstem, which then project widely throughout the cortex
- Serotonin has diverse functions: implicated in the modulation of mood and sleep, as well as body temperature, appetite and metabolism
- Drugs used in the treatment of depression and anxiety act specifically on serotonergic neurons, and tryptophan depletion lowers mood and causes relapse of depression in at-risk groups
18
Q
Glutamate
A
- The major neurotransmitter for excitatory neurons is glutamate, and it is estimated that over half of all brain synapses release this agent.
- Glutamate binds to NMDA receptors and AMPA receptors, which control long-term potentiation (LTP)
- LTP = synaptic connections between neurons becoming stronger with frequent activation. LTP is thought to be a way in which the brain changes in response to experience ⇒ learning and memory
19
Q
GABA
A
- Most inhibitory neurons in the brain and spinal cord use either GABA or glycine as a neurotransmitter.
- As many as one-third of the synapses in the brain use GABA as their neurotransmitter
20
Q
Neuropeptides
A
- Neuropeptides are small protein-like substances produced and released by neurons present in tissues at much lower concentrations than conventional neurotransmitters released from large dense core vesicles
- Most synapses use both conventional neurotransmitters and neuropeptides
- Main categories include: brain/gut peptides, opioid peptides, pituitary peptides and hypothalamic releasing hormones
- Longer-chain molecules, compared to conventional neurotransmitters
- Neuropeptides typically produce neuronal responses with slow onset and long duration → G-protein coupled receptor
- Can act as neuromodulators since their effects are to potentiate or depress the effects of a second transmitter
21
Q
Substance P
A
- Brain/gut peptide
- Hippocampus, amygdala, and GI tract
- Vasodilator, Involved in pain signalling, ‘First line’ defense system
- Released in response to noxious/extreme stimuli (stressors)
- E.g. to toxicants/poisons, activates the vomiting center in the medulla
22
Q
Opioid peptides
A
- Opioid peptides are widely distributed throughout the brain and are often co-localized with other small-molecule neurotransmitters such as GABA and 5-HT. Opioid peptides act at three distinct types of opioid receptors, namely, μ-, δ-, and κ-opioid receptors.
- In general, these peptides tend to be depressants: pain relief, anxiety suppression, leading to feelings of well being.
- 3 main classes: endorphins, enkephalins, dynorphins.
- Endorphins are produced by the pituitary gland in response to pain and stress
- But their release can also be triggered by exercise, spicy food, chocolate, sex
- Opioids are also involved in complex behaviors such as sexual attraction and aggressive/submissive behaviors.
23
Q
Receptor
A
Membrane protein with binding sites for a neurotransmitter
24
Q
Pharmacology of binding sites
A
Which transmitters affect them and how drugs interact with them
25
Q
Kinetics of the transmitter binding process
A
The duration of the effect
26
Q
Selectivity of the ion channel
A
Excitation or inhibition
27
Q
Conductance
A
Magnitude of the effects
28
Q
Affinity
A
Ability to bind with a particular transmitter
29
Q
Divergence
A
Each neurotransmitter has multiple receptors
30
Q
Inactivation of neurotransmitters
A
Various mechanisms for NT removal from the synaptic cleft:
- Transport
- Deactivation by enzymes e.g. acetylcholinesterase
- Diffusion
