1
Q
What are the three main stages of cell signalling
A
reception- receive signal in form of neurotransmitter
transduction- converted to electrical
response- cell responds
2
Q
Two types of cell signal
A
electrical
chemical
3
Q
process of cell signalling (4 steps)
A
- neurone sends electrical signal down axon
- at end of axon, electrical signal changes to chemical
- axon releases the chemical signal in the form of a neurotransmitter into the synapse
- NTs move signal through synapse to neighbouring dendrite which converts chemical signal to electrical
4
Q
two results of cell signalling
A
excitation or inhibition
5
Q
What are neurotransmitters
A
chemical messengers released by neurones
6
Q
neurotransmitters have to fit into three criteria:
A
- be synthesised and stored in presynaptic neurones
- be released by presynaptic axon terminal
- produce response in postsynaptic cell, they function at the synapse
7
Q
cycle of neurotransmitters (4)
A
synthesis- NTs are produced within a neurone and are packaged into vesicles for release
release- NTs are released into synapse
receptor binding- NTs travel through the synapse and binds to the receptors on the target cell altering electrical properties
termination of action- NTs are quickly removed from the synaptic cleft through degradation or re-uptake.
8
Q
Presynaptic terminal
A
the end of an axon that forms a synapse
9
Q
Secretory vesicles
A
vesicles larger than synaptic vesicles that contain neuropeptides and neuromodulators released from the axon terminal to activate receptors on surrounding neurones, they are related when a neurone is repeatedly stimulated.
10
Q
Function of neuropeptides and neuromodulators
A
released contents act on metabotropic receptors on target cells and modulate or enhance the effects of neurotransmitters.
effects are slower and longer lasting than synaptic vesicles
11
Q
Synaptic cleft
A
the area between the presynaptic terminal and the post synaptic regions
12
Q
synaptic vesicles
A
small vesicles that contain, carry and release neurotransmitters
13
Q
A
14
Q
Active zone
A
the part of the presynaptic regions where synaptic vesicles dock and are released
15
Q
Postsynaptic density
A
a region of the postsynaptic membrane enriched with receptors
16
Q
chemicals within a presynaptic terminal (4)
A
- neurotransmitters and the enzymes required for their synthesis
- vesicular transporters
- reuptake transporters
- degradative enzymes
17
Q
vesicular transporters
A
proteins which transport neurotransmitters into the synaptic vesicles
18
Q
reuptake transporters
A
proteins which take or transport the released neurotransmitters back into the presynaptic terminal
19
Q
degradative enzymes
A
they break down any free neurotransmitter
20
Q
Chemicals in the postsynaptic region
A
receptors
second messengers
21
Q
Second messengers
A
these are small signalling molecules inside the cell that carry and amplifies a signal from a receptor to the target molecules inside the cell
22
Q
what are ligands
A
molecules that binds to receptors
23
Q
What are agonists
A
ligands that activate receptors
24
Q
What are antagonists
A
ligands that binds to receptors but do not activate them, instead they block the site so other agonists can’t activate it
25
ionotropic receptors
their activation results in the passage of ions through the cell membrane
- causes opening of ion channels
they mediate fast synaptic neurotransmission
26
Effects of ionotropic receptors
movement of ions influences the membrane potential
if ions are positive --> depolarisation (excitatory)
if ions are negative --> hyperpolarisation (inhibitory)
27
Metabotropic receptors
their activation leads to intracellular metabolic pathway signalling
belong to the family of G-protein coupled receptors
coupled to intracellular regulatory proteins
binding initiates an intracellular biochemical cascade which generally results in the increase or decrease of other intracellular proteins or calcium levels.
slow synaptic neurotransmission
28
What are G proteins
molecular switches inside cells that help transmit signals from receptors on the cell surface (metabotropic receptors) to internal signalling pathways
29
G-Protein coupled receptors (GPCRs)
meaning they used G proteins as a way of transmitting the signal into the cell and influencing other proteins such as enzymes of ion channels to trigger second messengers such as cAMP
30
What is glutamate
the major excitatory neurotransmitters throughout the nervous system, expressed in almost all brain regions
the binding of glutamate to its receptors causes excitation of neurones--> they are more likely to fire action potentials
31
Classes of glutamate receptors
Ionotropic
- AMPA
- NMDA
metabotropic (mGluR)
32
AMPA
glutamate receptor
fast synaptic transmission
Na+ influx and K+ efflux
sometimes Ca2+
33
NMDA
glutamate receptor
they conduct Na+, K+
they are voltage and ligand gated
34
What is the precursor molecule of glutamate
glutamine
35
What is a precursor molecule
starting or parent compound that is transformed into another molecule, often a more active or specialised product
36
What is the enzyme that deaminates glutamine
glutaminase
37
Glutaminase equation
glutamine --> glutamate + ammonia
catalysed by glutaminase
38
Glutamate to glutamine enzyme
glutamine synthase
39
Glutamine cycle in the brain (5 steps)
1. glutamate is released into synaptic cleft
2. glutamate is then taken up by glial cells
3. in glial cells glutamate is converted back into glutamine using glutamine synthase
4. glutamine is transported back to neurone
5. in the presynaptic neurone, glutamine is converted back into glutamate and the cycle begins again
40
Glutamate importance for health
important for different forms of learning and memory because it is the main excitatory neurotransmitter in the brain and plays a central role in synaptic plasticity
41
What is a synaptic plasticity
the process by which synapses strengthen or weaken over time in response to activity
42
Glutamate in disease
dysregulation of glutamate activity can lead to excessive excitability of neurones which can cause seizures and even epilepsy
excitotoxicity can happen in stroke because of ischemia and ion pumps fail
43
what is GABA
the major inhibitory neurotransmitter in the brain
44
what is the precursor molecule to GABA
glutamate
45
three classes of GABA receptors
GABA-A
GABA-B
GABA-C
46
GABA synthesis enzyme
glutamic acid decarboxylase
47
GABAA R description and action
ionotropic receptors
produce rapid, short-lived inhibitory responses
expressed in CNS- brain and periphery
When two GABA molecules bind to the receptor: receptor triggers opening of Cl- selective pores. Cl- influx makes the inside of the neurone more negative so there is a lower change of action potential
48
GABAB R type and function
G-protein coupled receptors/metabotropic
produces slow and prolonged inhibitory responses
expressed in CNS- brain and periphery
when GABA binds to the receptor it causes:
- K+ channels to open and K+ flow out of the cell
- neurone hyperpolarisation contributing to its inhibition
49
What are benzodiazepines
medication for anxiety and alcohol dependance
their target is GABAA R
50
What are catecholamines
organic compounds comprised of a catechol ring and a side chain amine.
a catechol ring with two hydroxyl groups
51
what are the catecholamine neurotransmitters
dopamine, noradrenaline and adrenaline
52
dopamine is in what areas of the brain
substantia nigra
ventral tegmental area
hypothalamus
53
where is dopamine in the periphery
pancreas
liver
cardiovascular system
54
Roles of dopamine in the brain
neurotransmission
motor control
reward circuitry
cognition
55
Dopamine is associated with these disorders
schizophrenia
parkinsons disease
drug addiction
neuropsychiatric disorders
56
Biosynthesis of dopamine
Tyrosine + TH --> DOPA
L-DOPA + AADC --> dopamine
57
Enzymes involved in biosynthesis of dopamine
TH- tyrosine hydroxylase
AADC- aromatic L-amino acid decarboxylase
58
What are catabolic enzymes
enzymes that catalyse the breakdown of complex molecules into simpler ones
59
Dopamine transporters (DAT)
on presynaptic neurone membrane
clears DA from synaptic cleft by transporting it back to the presynaptic neurones
- deregulation of DAT leads to neuropsychiatric disorders like depression or Parkinson's
60
Dopaminergic synapse
in presynaptic terminal of dopaminergic neurones, tyrosine is transformed into L-DOPA by the action of tyrosine hydroxylase
L-DOPA is converted to dopamine by action of DOPA decarboxylase
DA is then transferred in vesicles by VMAT2 transporter
after exocytosis of the DA vesicles, DA binds to the DA receptors on the post synaptic membrane, leading to the transduction of the signal in the postsynaptic membrane
DA is then recycled by re-uptake via the DA transporter (DAT) or catabolised by the action of monoamine oxidase.
61
D1-like dopamine receptors
D1 and D5
coupled to Gs (type of G protein)- stimulatory signalling
activates adenylyl cyclase
increase [cAMP] levels
62
D2 like receptors
D2,D3,D4
coupled to Gi/o- inhibitory signalling
activates adenylyl cyclase
increase [cAMP] levels
63
Levodopa
medication that targets all D5 receptors
increases dopamine
Parkinsons
64
Antipsychotics
e.g, haloperidol, clozapine etc
target D2 receptors
antagonists
treat psychosis, schizophrenia and bipolar
65
Major noradrenergic nuclei
locus coeruleus
66
Noradrenergic receptors
alpha 1+2
beta 1,2+3
all are metabotropic
67
Role of noradrenaline in brain function
arousal (how awake you are)
memory and condition
stress response
68
Noradrenaline synthesis
DPH (dopamine beta hydroxylase) converts DA to NA
PMT converts noradrenaline to adrenaline
69
A typical NA synapse
NA synthesis is performed from dopamine through DBH and transported into a synaptic vesicle by a vesicular monoamine transporter (VMAT2)
after NA is released into the synaptic cleft it binds to specific adrenergic receptors to activate the signalling for the specific task
70
Alpha 1- adrenoreceptors
excitatory
vascular smooth muscles, blood vessels, gastrointestinal system, kidneys, brain, uterus, eyes and bladder
muscle contraction
71
Alpha 2- adrenoreceptors
inhibitory
presynaptic neurones
brain, pancreas, heart
inhibits neurotransmitter release
72
Beta 1,2 and 3 adrenoreceptors
generally excitatory
brain, heart, liver, pancreas, smooth muscle, lungs
73
Propranolol
Beta 1 and 2 adrenoreceptors
antagonist
hypertension, angina, anxiety
74
Phenylephrine
alpha 1 adrenoreceptor
agonist
hypotension
nasal congestion
75
What is the ester neurotransmitter
acetylcholine
76
functions of acetylcholine in CNS
Cholinergic neurones
neuroendocrine function
learning, memory, cognition
regulation of REM sleep cycles
77
Function of acetylcholine in PNS
regulation of muscle movements
heart rate
gut mobility
78
Acetylcholine producing neurones in the brain
nucleus basal
the medial septal nucleus and diagonal band
pedunculopontine nucleus
79
CAT (choline acetyltransferase)
the enzyme that synthesises acetylcholine from choline and acetyl-CoA creating CoA as a by-product
80
AChE (acetylcholinesterase)
the enzyme that breaks down acetylcholine after its released into the synaptic cleft (a critical step in ending its neurotransmission)
81
Nicotinic ACh receptors
ionotropic
5 sub-units
muscular and neuronal
fast brief responses
post-synaptic
excitatory
82
muscarinic ACh receptors
GPCRs- metabotropic
slow prolonged response
pre and post synaptic
can be excitatory or inhibitory
83
mAChRs in CNS
hippocampus
hypothalamus
striatum
cortex
substantia nigra
84
mAChRs periphery
gastrointestinal tract
urinary bladder
salivary glands
heart
lungs
airway
pancreatic beta cells
85
Co-expression of mAChRs
meaning that multiple receptor subtypes can be expressed in the same cell and can interact functionally
86
M1 function
memory, learning and cognition
87
M2 function
inhibitory receptors, decreased response to cholinergic stimuli, cardiac myocyte control
88
M3 function
smooth muscle contraction, glandular secretion, promotion of insulin release
89
M4 function
regulation of locomotor activity (voluntary movement from one location to another), analgesia (reduction of pain perception
90
M5 function
regulation of dopamine transduction in VTA (Area in brain), role in drug addiction
91
M1 therapeutic relevance
learning and memory deficits, cognitive disorder and Alzheimer disease
92
M2 therapeutic relevance
urinary bladder disorders and CVD
93
M3 therapeutic relevance
GI tract disorders and appetite modulation
94
M4 therapeutic relevance
psychosis, schizophrenia, potential modulator of reward circuitry
95
M5 therapeutic relevance
drug addiction, drug withdrawal symptoms
96
methacholine
medication that treats asthma
targets mAChRs: all M receptors but mainly M2 and M3
97
what are the Indolamines
serotonin
98
Main serotonin producing nuclei in the CNS
a collection of Raphe nuclei in the midbrain and pons
99
Shortened name for serotonin
5HT
100
5HT receptors
there are 7 subclasses and 14 known receptors all metabolic except 5HT3
5HT1-7
101
functional role of 5HT in brain function
diverse including: reward, pain, emotion, cognition, learning and memory
also regulated mood sleep and appetite
102
Synthesis of 5HT
step 1: hydroxylation
the enzyme tryptophan hydroxylase (TPH) converts tryptophan --> 5HTP
step 2: decarboxylation
the enzyme AAAD or DOPA converts 5HTP to 5HT (serotonin)
103
What is the precursor molecule to serotonin
amino acid tryptophan
104
what is VMAT
vesicular monoamine transporters
a protein responsible for transporting monamine neurotransmitters from the cytoplasm into synaptic vesicles for stage and subsequent release
105
A typical serotonin synapse
1. at rest serotonin is stored in vesicles in pre-synaptic neurones
2. when neurone is stimulated, serotonin is released into the synapse
3. binds to post-synaptic neurone receptors to include a nerve impulse
4. binds to auto-receptors on pre-synaptic neurone, to regulate the synthesis and release of serotonin
5. serotonin is taken back into the neurone to stop its action
6. reused of broken down by monoamine oxidase
105
Antidepressants
monoamine oxidase inhibitors prevent breakdown of serotonin: increases levels in the brain
tricyclic antidepressants- inhibit the reuptake of both serotonin and NE
SSRIs- selectively inhibit the re-uptake of serotonin
106
Anxiolytics
azapirone anxiolytics like buspirone and trandospirone act as 5HT1A receptor antagonists
107
Antipsychotics
some binds to and modulate serotonin receptors, contributing to the therapeutic effects
108
Psychedelics
agonists of serotonin receptors, causing hallucinogenics
psilocybin- 'magic mushrooms'
LSD- a synthetic psychedelic that alters perception mood and cognition
mescaline- hallucinogenic
109
sertraline
an SSRI antidepressant
110
enzymes for glutamate
biosynthesis- glutaminase
catabolism- glutamine synthase
111
Enzymes for GABA
biosynthesis- glutamic acid decarboxylase
catabolism- GABA-transaminase (GABA-T)
112
enzymes for dopamine
biosynthesis- tyrosine hydroxylase (TH), aromatic amino acid decarboxylase (AADC)
catabolism- monoamine oxidase (MAO),catechol-O-transferase (COMT)
113
Enzymes for noradrenaline
biosynthesis- dopamine beta-hydroxyalase (DBH)
catabolism- MAO, aldehyde dehydrogenase
114
Enzymes for serotonin
biosynthesis- tryptophan hydroxylase (TPH), AADC
Catabolism- MAO, aldehyde dehydrogenase
115
Enzymes for acetylcholine
biosythesis- choline acetyltransferase
catabolism- acetylcholinesterase
116
biosynthesis vs catabolism
biosynthesis is creating bigger molecules from smaller ones
catabolism is breaking down large molecules into smaller ones
117
GABA catabolism
two step pathway known as the GABA shunt
1. GABA--> succinct semialdehyde
enzyme- GABA-T
2. succinct semialdehyde--> succinate
enzyme- semialdehyde dehydrogenase
succinate then enters TCA cycle
118
glutamate transporters
vesicular- VGLUT- vesicular glutamate transporter
re-uptake- glutamate re-uptake transporter or excitatory amino acid transporter (EAAT)
119
GABA transporters
vesicular- VGAT vesicular GABA transporter
re-uptake- GAT GABA transporter
120
Dopamine transporters
veiscular- VMAT2 vesicular monoamine transporter
re-uptake- DAT
121
noradrenaline transporters
vesicular- VMAT2
Re-uptake- NERT norepinephrine
122
serotonin transporters
Vesicular- VMAT2
reuptake transporters- SERT
123
acetylcholine transporters
vesicular- VAchT
re-uptake- none
124
why does acetylcholine have a reuptake transporter
acetylcholine is broken down by AChE in the synaptic cleft and the resulting choline is then transported back into the neurone by the high affinity choline transporter to be reused for Ash synthesis.
125
Haloperidol GPCR targets
dopamine- strong antagonist at D2R
serotonin- weak antagonist at 5-HT2AR
acetylcholine- minimal action
126
clozapine GPCR targets
dopamine- moderate antagonist at D2R
serotonin- antagonist at 5-HT2AR; partial agonist at 5-HT1AR
acetylcholine- antagonist at M1-M5 receptors
127
olanzapine GPCR target
dopamine- antagonist at D2R
serotonin- strong antagonist at 5-HT2AR, 5-HT2CR
acetylcholine- antagonist at M1 receptor
128
aripiprazole GPCR targets
dopamine- partial agonist at D2R
serotonin- partia agonist at 5-HT1AR and agonist at 5-HT2AR
acetylcholine- weak/minimal action
129
antipsychotic drugs as acetylcholine antagonists
many serious side effects of clozapine and olanzapine arise from their antagonist activity of muscarinic receptors; anticholinergic activity results in dry mouth, constipation, sedation (M1), confusion and cognitive decline
130
Neuroscience
flashcards
Decks in class (14)
# Cards
-
Neurones54
-
Glia41
-
Neurotransmitters131
-
Neurophysiology31
-
G-protein coupled receptors65
-
Anatomy of the brain52
-
Anatomy of the brain: 248
-
Anatomy of the spinal cord44
-
Autonomic nervous system32
-
Acetyl choline neurotransmission3
-
Acetyl choline transmission67
-
Noradrenaline transmission46
-
Enzymes47
-
Enzyme kinetics27
