Neurotransmitters Flashcards

1
Q

What does neurotransmission require?

A

release of neurotransmitters and interaction with post synaptic receptors

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2
Q

What are the 3 phases of synaptic transmission?

A

1 - transmitter synthesised, packaged and released from 1st cell into synapse

2 - synaptic activation of 2nd cell, signal integration and signal conduction

3 - inactivation of NT

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3
Q

What are the key traits of neurotransmitter?

A

rapid (2ms/200micros) - chemical transmission allows rapid transmission of lots of info over small area of contacts

diverse
adaptable
plastic
learning and memory

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4
Q

What is found on dendrites?

A

protrusions (spines)

that increase number of possible inputs to a nerve cell

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5
Q

What is the function of inputs into integrator (soma/cell body)?

A

modify upstream inputs

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6
Q

Synapse distance?

A

synapse represents a high resistance for electrical transmission - need chemical NT

20-100nm

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7
Q

What is the action potential?

A

wave of depolarisation that causes depolarisation of nerve terminal to trigger NT release

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8
Q

What are the 3 types of NT?

A

amino acids (glutamate - major excitatory, GABA - major inhibitory, glycine)

amines (noradrenaline, dopamine, ACh)

neuropeptides (opioid peptides)

mediate rapid (micros-ms) or slower (ms)

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9
Q

What does transmitter release require?

A

increase in intracellular Ca (100microM)

transmission restricted to specialised structure (asymmetric synapse - lots of presynaptic NT vesicles)

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10
Q

How can rapid release of NT occur?

A

vesicular proteins /presynaptic membrane proteins

  1. synaptic vesicles are filled with NT are PRIMED
    - a helical tails of proteins overlap to form supercoils which are active
  2. interaction between vesicles and synaptic membrane proteins allows rapid response - complex docked in synaptic zone
  3. Ca channels are close to primed vesicles - Ca sensor in protein complex is activated by Ca entry and causes conformational change in complex
  4. Promotes fusion with membrane and opening of pore to release NT - EXOCYTOSIS
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11
Q

What targets vesicular proteins?

A

neurotoxins

tetanus toxin - target vesicular proteins, paralysis

botulinum toxin - target vesicular and membrane proteins, flaccid paralysis

alpha latrotoxin - deplete NT release by stimulating exocytosis

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12
Q

What are tetanus and botulinum toxins?

A

Zn dependent endopeptidases that inhibit transmitter release

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13
Q

What 3 things does transmitter release require?

A
  • vesicles to be docked on presynaptic membrane
  • protein complex formation to enable rapid response to Ca entry
  • ATP and vesicle recycling
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14
Q

What is special about synaptotagmin?

A

Ca sensor

part of it is embedded in vesicle to allow NT sensitivity and release

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15
Q

What defines neurotransmitter action?

A
post synaptic receptor kinetics
1 - ION CHANNEL RECEPTOR
fast (micro to msecs)
all excitatory/inhibitory transmission
(Na+)

2 - G PROTEIN COUPLED RECEPTOR
slow (s/min)
effectors may be enzymes -a adenyl cyclase, PLS, cGMP-PDE) or channels (Ca/K)

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16
Q

Examples of ion channel receptors?

A

CNS
glutamate - Na, depolarisation of membrane
GABA/Gly - Cl-, hyperpolarised

NMJ
ACh at nicotinic receptors

17
Q

Examples of G protein coupled receptors?

A

CNS and PNS:

ACh at muscarinic receptors
dopamine
noradrenaline
5HT
neuropeptides (encephalin)
18
Q

Where is glutamate and GABA typically found?

A

glutamate - dendritic spines
causes increase in membrane potential

GABA - soma (can inhibit as it is downstream)
hyperpolarises potential - more negative (greater distance to threshold)

19
Q

What are the different glutamate receptors?

A

ALL 4 SUBUNITS

AMPA receptor (Na) - most fast excitatory synapses

NMDA receptor (Na and Ca) - only operates on already depolarised cell

slow component of excitatory transmission for coincidence/learning mechanisms

20
Q

What is the effect of Ca on AMPA receptor?

A

modifies the receptor to potentiate its response (depolarisation of post synaptic membrane)

activates protein synthesis that modifies synapse formation

21
Q

Describe reuptake of NT glutamate from synapse?

A

use excitatory amino acid transporter (EAAT) that is abundant in glial cells

  • take glutamate to glial cell
  • metabolised using glutamine synthetase to form glutamine

OR
EAAT also on nerve terminal
- use glutamate to refill synaptic vesicles

22
Q

What is associated with excess glutamate in the synapse?

A

abnormal cell firing leading to seizures (epilepsy)

as glutamate [] decreases, glutamine increases

23
Q

What is epilepsy?

A

affects 50 million worldwide - most common neurological condition, 30% refractory by treatment

characterised by recurrent seizures due to abnormal neuronal excitability

24
Q

What is the difference in structure between glutamate and GABA?

A

GABA lacks COOH group which would form glutamate

25
Q

What enzyme converts glutamate to GABA?

A

glutamic acid decarboxylase
(GAD) - (B6)
highly concentrated in nerve terminals and GABA neurones

26
Q

What does GABA do to cell firing?

A

increases threshold to cause a depolarisation

INHIBITORY NT

27
Q

What is the GABA receptor?

A

GABAaR

28
Q

What transporter involved in the transport of GABA from synaptic cleft?

A

GABA transporter (GAT) on glial cell/post synaptic membrane

29
Q

What enzyme metabolises GABA to succinate semialdehyde?

A

GABA transaminase (GABA-T) in glial cell

succinate to TCA cycle

30
Q

Describe the structure of GABA receptor?

A

5 subunits - pentameric

drugs that modulate activity of GABA receptor to enhance GABA transmission (antiepileptic, sedative, muscle relaxant, anti-anxiety )
- facilitate GABA transmission by enhancing ongoing hyperpolarisation

31
Q

How do drugs that facilitate GABA transmission work?

A

Cl- channel opens after GABA binds

Cl- channel modified at allosteric sites

32
Q

What is benzodiazepine?

A

acts on site of complex to affect frequency of channel opening when activated by GABA

enhances ongoing inhibition by GABA

33
Q

What are barbiturates?

A

act on different site of GABA receptor

increase open time of reponse

34
Q

Epilepsy treatment?

A

dampen down excitatory activity by facilitating inhibitory transmission

drugs target GABA synapse