Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Biomembranes > Inhibitory Transmission > Flashcards

Inhibitory Transmission Flashcards

1
Q

What is the GABA A receptor

A
  • a transmitter gated anion channel
  • pentamer
  • major inhibitory receptor
  • mediates “fast” inhibition in spinal cord alongside glycine
  • proconvulsant and anxiogenic (panic)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What drugs act on GABA A receptor

A
  • positive allosteric modulators (PAMs), e.g. diazepam
  • target for general anaesthetics
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is the GABA B receptor

A
  • a GPCR
  • heterodimer
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What drugs act on GABA B receptor

A
  • Baclofen
  • selective agonist used to treat muscle stiffness arising from multiple sclerosis and spinal cord injuries
  • acts on spinal cord
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is GABA-T

A
  • GABA transaminase
  • converts alpha-ketoglutarate to glutamate in step 1 of inhibitory GABA-ergic transmission
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is GAD

A
  • glutamic acid decarboxylase
  • converts glutamate to GABA in second step of inhibitory GABA-ergic transmission
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What blocks the GABA transporters GAT 1-3

A

tigabine (anti-convulsant)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is VGAT

A
  • vesicular GABA amino acid transproter
  • vacuums and concentrates GABA in vesicles
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Describe feed-forward inhibition

A
  • invovles bi-synaptic inhibitory response
  • activation of glutamate-gated cation conducting channels produce an excitatory postsynaptic potential (EPSP)
  • activation of GABA-gated anion conducting channels produce an inhibitory postsynaptic potential (IPSP)
  • control firing rate of neurons
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Describe feed-back inhibition

A
  • firing of the pyramidal neuron activates inhibitory interneuron, which inhibits pyramidal neuron
  • once inhibition decays pyramidal neuron can fire again
  • circuits can generate neuronal oscillations (rhythmic activity) involving coordinated activity of principle neurons and interneurons
  • interfering with balance causes dramatic effects on learning and memory
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What does the Gi alpha subunit do

A

inhibits adenylate cyclase (AC) activity to decrease cAMP levels

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Effects of postsynaptic GABA B activation

A

causes Gi BY complex to open K+ channel, causing slow hyperpolarisation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Effects of presynaptic GABA B activation

A

causes Go BY complex to decrease the probability of voltage-gated Ca channel opening, and therefore decreases quantal release of neurotransmitter

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Define the term “phasic inhibition”

A

mediated by synaptically-localized receptors with a low affinity for GABA, results in a transient, rapidly desensitizing GABAergic conductance

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Role of B1 GABA B receptor subunit

A

provides GABA binding domain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Role of B2 GABA B receptor subunit

A

provides G-protein coupling to G-alpha-i and G-alpha-o

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

The GABA A receptor can be used as a therapeutic target for which drugs

A
  • hypnotic and anxiolytic drugs
  • benzodiazepines
  • barbiturates
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

How do benzodiazepines and barbiturates act on GABA A receptor

A
  • benzodiazepines increase probability of channel opening (energetically unstable state)
  • barbiturates promote channel open states of long duration
  • barbiturates at higher concentrations directly activate the receptor
  • at high doses, barbiturates, propofol and etomidate induce an anaesthetic state, whereas benzodiazepines do not
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Using Xenopus laevis to close GABA A receptor subunits

A
  • led to unexpected diversity of subtypes
  • 19 different subunits in brain
  • rules governing which subtypes can get together with who and are located in different parts of brain
  • alpha1-6
  • gamma 1,2
  • beta 1-3
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Receptor isoforms of GABA A

A
  • distinct physiology, pharmacology, and exhibit a heterogeneous expression pattern in the CNS
  • not uniformly expressed, found in various locations throughout nervous system
21
Q

Diazepam enhances the function of which GABA A receptor subunits

A
  • alpha1, alpha2, alpha3, alpha5
  • H residue at position 101
  • alpha4 and alpha6 have R residue at this position
22
Q

Mutation of R101 to H on alpha6 subunit

A

produces a diazepam-sensitive receptor

23
Q

What was found in the alpha1H101R mouse

A
  • alpha1 mutation causes loss of 3H-flumazenil binding in areas known to express alpha1 subunit
  • dizaepam is not sedative, but anxiolytic
24
Q

Diazepam in alpha2H101R mouse

A

no longer anxiolytic but is sedative

25
Q

How do general anesthetics produce side effects

A
  • act on neuronal membrane
  • enhance GABA A receptor function
26
Q

Where is the GABA recognition site on GABA A receptors

A

between alpha and beta subunits

27
Q

Where is the benzodiazepine binding site on the GABA A receptor

A
  • between alpha and gamma subunits
  • not at GABA recognition site, so does not open channel
28
Q

Beta subunnit “knock in” anaesthetic-insensitive mice

A
  • Etomidate is selective for GABA A receptors incorporating B2, B3 subunits
  • beta subunit specificity dictated by single amino acid located in TM2
29
Q

Effects of etomidate (anaesthetic agent) on a B2 N265S mutation

A

reduced GABA A receptor enhancing effects, prevented sedative effects, impaired hypotic action

30
Q

Effect of etomidate and propofol on the B3 N265M mutation

A

reduced GABA A receptor enhancing effects and greatly impaired hypnotic action

31
Q

What are neurosteroids

A

endogenous positive allosteric modulators (PAMs) of the GABA A receptor

32
Q

What evidence suggests that neurosteroids made in the CNS act to influence neural inhibition and behaviour

A

Administration of neurosteroids to rodents produced anxiolytic, analgesic, anticonvulsant and sedative behaviours

33
Q

How can neurosteroids fine-tune neural inhibition to influence mood and behaviour

A
  • anxiolytic
  • sedative
  • hypnotic
  • analgesic
  • anticonvulsant
  • antidepressant
34
Q

GABA A receptor alpha2 Q241W mouse

A
  • impairs neurosteroid enhancement of GABA responses mediated by alpha2-GABA A receptors
  • inhibitory GABA A receptor-mediated mIPSCs in the hippocampus of the exhibits a reduced duration
  • exhibits anxiogenic phenotype and exhibits reduced sensitivity to anxiolytic effects of 5alpha3alpha
  • presence of neurosteroid tone sufficient to influence synaptic alpha2-GABA A receptors and behaviour
35
Q

Brexanolone (neurosteroid) in pregnancy

A
  • Animal studies have revealed evidence of decreased body weight, decreased pup viability, developmental toxicity, female offspring neurobehavioral deficit, lower pup survival, post-implantation loss, reproductive toxicity
  • PPD associated with reduced expression of GABA A receptors
  • causes sedation and can go unconscious -> infused with IV for 60 hours
36
Q

What is the strychnine-sensitive glycine receptor (nAChR family) responsive to

A
  • propofol
  • glycine, tauring, strychnine
  • volatile anaesthetics and alochols
37
Q

What is GlyT1

A

astrocytic glycine transporter

38
Q

What is GlyT2

A

neuronal glycine transporter

39
Q

What is VIAAT

A

vesicle inhibitory amino acid transporter

40
Q

What is strychnine

A
  • obtained from poisonous nuts of the strychnine-tree
  • potent competitive antagonist
  • enhances perception of pain
  • causes convulsions
41
Q

Effects of mutations of the glycine receptor

A
  • hyperekplexia (startle reaction)
  • neonatal hypertonia
  • variable incidence of apnoea
  • intellectual disability and delays in speech acquisition
42
Q

Define the term “tonic inhibition”

A

mediated by extrasynaptic receptors with a high affinity for GABA, results in a persistent GABAergic conductance

43
Q

Role of GABA in mediating feed-forward inhibition

A

GABA limits window for generation of AP as it arrives only 1-5msec after glutamate input

44
Q

Which subunit of GABA A receptor is responsible for sedation

A

alpha1

45
Q

Which subunit of GABA A receptor is responsible for anxiety

A

alpha2 or alpha3

46
Q

Side effects of Benzodiazepines

A
  • drowsiness, dizziness, decreased concentration, impairment of motor coordination
  • mild muscle relaxation as result of action on spinal cord, cerebellum, and brain stem
47
Q

Side effects of Barbiturates

A
  • dizziness, lightheadedness, sedation, memory and attention impairments
48
Q

Binding site of Barbituates

A

alpha or beta subunit

49
Q

Why must doses of Barbiturates be closely monitored

A
  • at high doses, can mimic GABA and act directly on GABA receptors, causing profound nervous system depression
  • toxic dose is not much higher than therapeutic dose (narrow therapeutic index)

Biomembranes (12 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions