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inhibitory transmission Flashcards

(52 cards)

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1
Q

what is GABAaR

A

a transmitter gated anion channel which consists of 5 transmembrane subunits

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2
Q

what is GABAbR

A

a G-protein coupled receptor consisting of 2 subunits

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3
Q

what is the major inhibitory receptor in the mamallian brain

A

GABAaR

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4
Q

what is fast inhibition in the spinal cord mediated by

A

GABAaRs and glycine receptors

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5
Q

what are GABAaR inhibitors

A

proconvulsant and anxiogenic

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6
Q

what are drugs that enhance GABAaR function called

A

positive allosteric modulators (PAMs)

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7
Q

what is an example of a PAM

A

diazepam

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8
Q

what is the function of PAMs

A

anticonvulsant, anxiolytic, sedative and analgesic

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9
Q

do PAMs work in the absence of GABAaR

A

no

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10
Q

how do PAMs work

A

they enhance the effects of GABA whilst binding to a different part of the pentamer

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11
Q

describe the GABAbR

A

a heterodimer with GABAb1 providing the GABA binding domain and GABAb2 the G-protein coupling to Gai and Gao

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12
Q

what is baclofen

A

a slective GABAbR agonist used clinically to treat certain types of spacifity (muscle stiffness) reesultant from multiple sclerosis and spinal cord injuries
it is a skeletal muscle relaxant which acts on the spinal cord

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13
Q

how does GABA transmission work

A

a-ketoglutarate is made into glutamate by GATA-T
glutamate is made into GABA via GAD
GABA is backagaed by VGAT and then released into the synapse via exocytosis
the GABA attaches to GABAaR to cause hyperpolarisation

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14
Q

what is the affinity of extra-synaptic receptors for GABA

A

very high affinity - constantly opening and closing i response to very small concs of GABA

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15
Q

GABARs that are directly on the post-synaptic membrane have…

A

low affinity for GABA

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16
Q

what is phasic inhibition

A

fast

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17
Q

what is tonic injibition

A

slow

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18
Q

what is feed-forward inhibition

A

Involves a bi-synaptic inhibitory response. (GABA) arrives only 1-5 msec after the monosynaptic excitatory (glutamate) input, thereby limiting the time window for the summation of excitatory inputs to generate an action potential

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19
Q

what does activation of glutamate-gated cation conducting channels produce

A

EPSP

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20
Q

what does activation of a GABA-gated anion conducting channel produce

A

IPSP (inhibitory postsynaptic potential)

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21
Q

how does feed-back inhibition work

Study These Flashcards
A

The firing of the pyramidal neuron activates an inhibitory interneuron, which in turn inhibits the pyramidal neuron. Once the inhibition decays , the pyramidal neuron can fire again.

22
Q

what does tge Gi a subunit do in a GABAb receptor

Study These Flashcards
A

inhibits adenylate cyclase (AC) activity to decrease cAMP levels

23
Q

what does postsynaptic GABAb activation cause

Study These Flashcards
A

causes the Gi bY complex to open a K+channel causing hyperpolarisation.

24
Q

what does pre-synaptic GABAb activation cause

Study These Flashcards
A

the Go BY complex to decrease the probability of voltage-gated Ca2+channels opening, thereby decreasing the quantal release of neurotransmitter

25
what is mediated by presynaptic GABAb receptors
auto-inhibition of GABA release
26
what does GABA act post-synaptically to do
activate chloride-conducting GABAaRs to produce a IPSP also, activate GABABRs (viaGo) to decrease the probability of Ca channel opening and consequently decrease GABA release upon a second stimulus also, activates postsynaptic G-protein coupled GABABRs (Gi). Activation of GABABRs causes the opening of a potassium channel leading to a further, but prolonged hyperpolarisation i.e. a prolonged IPSP
27
PAMs are...
anxiolytic, anticonvulsant, analgesic, amnestic, sedative/hypnotic, general anaesthetic
28
drugs that inhibit GABAaR function are...
pro-convulsant (in high doses) and anxiogenic
29
how do benzodiazapines effect channel opening
increase the probability of channel openings
30
what do barbiturates promote
channel open states of long duration
31
what do barbiturates do at high concentration
directly activate the receptor
32
what induces anaesthetic (unconscious) states at high doses
barbiturates, propofol and etomidate
33
in the human brain, how many different GABAaR subunits are there
19
34
which GABAaR subunits does diazepam enhance the function of
a1, a2, a3 and a5
35
which GABAaR subunits does diazepam not enhance the function of
a4 and a6
36
why does diazepam only enhance the function of some subunits
because it can only enhance function in the presence of a H residue at position 101
37
where do general anaesthetics work
non-specifically on the membrane
38
what effect does binding on the a1 subunit of the GABAaR have
sedation
39
what effect does binding on the a2, a3 subunit of the GABAaR have
anxiolytic/analgesic
40
what effect does binding on the a5 subunit of the GABAaR have
cognition (alzheimers)
41
what effect does binding on the b3 subunit of the GABAaR have
immobiloty/anaesthesia
42
what effect does binding on the b2 subunit of the GABAaR have
sedation/anaesthesia
43
how quickly does induction of general anaesthethia by progesterone metabolites work
rapidly
44
how do progesterone metabolites have such a rapid effect on brain activity
non-genomic effect the steroid
45
where do alcohol, antidepressants and GHB exert their effects
through neurosteroids
46
what do neurosteriods do
fine tune neural inhibition
47
what are strychnine-sensitive glycine receptors
anion-selective transmitter-gated ion channels
48
what do strychnine-sensitive glycine receptors regulate
respiratory rhythms, motoe control, muscle tone, sensory and pain processing
49
what is the strychnine-sensitive glycine receptor activated by
glycine taurine strychnine
50
what causes hyperekplexia
mutations of the glycine receptor
51
what are the most frequent mutations in the glycine receptor
R271L/Q
52
what do mutations of the glycine receptor do
decrease both glycine sensitivity and the single channel conductance

biomembranes (9 decks)

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