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Flashcards in Transmission in CNS Deck (49):
1

Structure of a neuron?

- dendrites (inout region)
- cell body (nucleus that stores DNA, protein synethsis etc)
- axon (main conduction unit, carries signals in action potential form)
- axon terminals (output region, neurotransmitter release)

2

What types of synaptic transmission are there?

Electrical or chemical (most are chemical)

3

What is the name of the gap between cells at a synapse?

Synaptic cleft

4

What is action potential?

depolarisation of the axon membrane in order to signal

action potential opens calcium ion channels at the presynaptic terminal to initiate the neurotransmitter process

5

What are the stages of an action potential?

- resting membrane potential around -70mV
- sodium channels open: depolarisation (approx + 30mV)
- sodium channels close
- potassium channels open - repolarisation
- potassium channels close on hyperpolarisation
- return to resting potential

6

What are the main things that happen at the synapse?

- synthesis
- storage
- release
- inactivation/reuptake

7

How is acetylcholine synthesised?

Acetyl Coenzyme A + choline, catalysed by choline acetyltransferase to produce acetylcholine and CoemzymeA

always in excess so enzyme is not saturated

8

What neurones is Choline acetyltransferase specific to?

Cholinergic ones

9

Where is acetylcholine stored?

in synaptic vesicles in the axonal membrane

10

How is acetylcholine released?

Arrival of action potential at axonal terminal causes a calcium ion influx, which triggers release of the vesicle contents

11

Which receptors does acetylcholine bind to?

Muscarinic (M1-5) and nicotinic

12

Structure of nicotinic receptors?

5 subunits
- alpha (1-10)
- beta (B2-B5)
- delta
- epsilon
-gamma

different combinations in different types of receptor

13

What are the two main types of nicotinic receptor?

Muscular and neuronal

14

Location and structure of muscular nicotinic receptors?

neuromusclar junctions

ααβεδ ligand gated ion channel

15

Location and structure of neuronal nicotinic receptors?

Autonomic ganglia, CNS

Various αβ subunits E.g. neuronal nicotinic receptor
- α4β2 and the α7 subtypes

16

Inactivation and reuptake of acetylcholine?

acteylcholine esterase breaks down into acetateion and choline

40-50% of the choline formed is taken back up into the presynaptic cell by a transporter specific to cholinergic cells

17

What is a neuromuscular junction?

chemical synapse between a motor neurone and skeletal muscle

18

How does acetylcholine induce a response in the post synaptic cell?

ligand gated ion channels - so allow infux of sodium ions and depolarisation to continue the action potential

19

How does depolarisation affect the muscle cell at the neuromuscular junction?

depolarisation triggers calcium ion entry into the muscle cell which causes contraction

20

What is myasthenia gravis?

autoimmune condition. produce antibodies that block or damage the acetylcholine receptors which prevents the muscle contracting

21

Which muscles are predominantly affected by myasthenia gravis?

facial muscles and those that control swallowing

22

What medications can be used for myasthenia gravis?

Pyridostigmine - prevent breakdown of acetylcholine (work best in mild cases)

23

How is dopamine synthesised?

- l-tyrosine to l-dopa by tyrosine hyroxylase
- l-dopa to dopamine by dopa decarboxylase

tyrosine hyroxylase is rate determining step

24

Where is dopamine stored?

in synaptic vesicles at the axonal terminal, released when action potential triggers influx of Calcium ions

25

Which receptors does dopamine bind to?

D1 family (D1 and D5) - excitatory
D2 family (D2, 3, 4) - inhibitory

26

How is dopamine deactivated?

Metabolised by two enzymes:
- Catechol-O-methyltransferase (COMT)
- Monoamine oxidase (MAO)

27

How does reuptake of dopamine occur?

Catecholamines have highly specific active transport mechanisms to remove transmitter from synapse into presynaptic terminal

Dopamine Transporter - DAT

28

What are the 4 dopamine pathways?

Nigrostriatal
Mesolimbic
Mesocortical
Tuberoinfundibular

29

What does the nigrostriatal pathway control?

Substantia nigrata to caudate and putamen (striatum)
Dorsal striatum: motor function (Parkinson's)
Associative striatum: learning, habituation, memory, attention, motivation, emotion, volition

antipsychotics can decrease dopamine and cause parkinsonism

30

What does the mesolimbic pathway control?

Vetral Tegmented Area (VTA) in midbrain to limbic regions associated with rewards, motivation, affect and memory

includes ventral striatum (nucleus accumbens), amygdala, hippocampus and medial frontal cortex

too much dopamine in this pathway leads to positive symptoms (hallucinations etc)

31

What is the mesocortical pathway?

VTA to frontal cortex (including dorsolateral prefrontal cortex). controls cognitive function, motivation and emotional resposne

too little dopamine in this pathway in schizophrenia leads to negative symptoms

32

What is the tuberoinfundibular pathway?

Tuberal region to median eminence (infundibular region at top of pituitary stalk)
inhibits prolactin release from pituitary (inverse relationship between dopamine and prolactin)

33

What does an agonist do at a receptor?

stimulate the receptor and mimic the natural ligand

34

What does an antagonist do at a receptor?

block the receptor and stop the effects of the natural ligand

35

What does a partial agonist do at a receptor?

unable to induce maximal activation of a receptor, regardless of the amount

36

What are some of the main types of receptor?

Ionotropic Receptors
Metabotropic Receptors
Kinase-linked Receptors
Intracellular Receptors

37

What are ionotropic receptors?

part of a ligand gated ion channel protein - activation causes changes in ion conductance

opened by neurotransmitters to allow passage of sodium ions (excitatory) or potassium or chloride ions (inhibitory)

examples: some receptors for acetylcholine, glutamate, and GABA

38

What are metabotropic receptors?

A receptor protein in the membrane, coupled to an effector via G proteins. a conformational change in the G protein activates enzymes needed for the effect

39

Speed of response of ionotropic receptors?

msecs, used in fast neurotransmission.

40

Speed of response of metabotropic receptors?

secs/mins/hours. used for slower neurotransmission processes (hormone, growth factors)

41

Speed of response of kinase receptors?

mins/hours

42

Speed of response of instracellular receptors?

long-lasting

43

How can the acetylcholine sysnthesis pathway be targeted by drugs?

Choline concentration determines rate, so increasing or restricting choline will increase or decrease

44

What type of drugs are used to treat schizophrenia?

antipsychotics: D2 receptor agonists

45

What type of drugs are used to treat parkinsons?

Dopaminergic drugs (precursors/agonists)

46

What type of drugs are used to treat Alzheimer's?

- Acetylcholinesterase inhibitors
- NMDA receptor antagonist

47

What kind of drugs are used to treat epilepsy?

GABA/glutamate transmission (anticonvulsants)

48

What kind of drugs are used to treat depression?

SSRIs

49

What is Parkinson's disease?

Loss of dopamine in the nigrostriatal pathway, diminished in the striatum. Dopamine's precursor (L-DOPA) is an effective treatment