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biomembranes > inhibitory transmission > Flashcards

inhibitory transmission Flashcards

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

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

A

inhibits adenylate cyclase (AC) activity to decrease cAMP levels

23
Q

what does postsynaptic GABAb activation cause

A

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

24
Q

what does pre-synaptic GABAb activation cause

A

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

25
Q

what is mediated by presynaptic GABAb receptors

A

auto-inhibition of GABA release

26
Q

what does GABA act post-synaptically to do

A

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
Q

PAMs are…

A

anxiolytic, anticonvulsant, analgesic, amnestic, sedative/hypnotic, general anaesthetic

28
Q

drugs that inhibit GABAaR function are…

A

pro-convulsant (in high doses) and anxiogenic

29
Q

how do benzodiazapines effect channel opening

A

increase the probability of channel openings

30
Q

what do barbiturates promote

A

channel open states of long duration

31
Q

what do barbiturates do at high concentration

A

directly activate the receptor

32
Q

what induces anaesthetic (unconscious) states at high doses

A

barbiturates, propofol and etomidate

33
Q

in the human brain, how many different GABAaR subunits are there

A

19

34
Q

which GABAaR subunits does diazepam enhance the function of

A

a1, a2, a3 and a5

35
Q

which GABAaR subunits does diazepam not enhance the function of

A

a4 and a6

36
Q

why does diazepam only enhance the function of some subunits

A

because it can only enhance function in the presence of a H residue at position 101

37
Q

where do general anaesthetics work

A

non-specifically on the membrane

38
Q

what effect does binding on the a1 subunit of the GABAaR have

A

sedation

39
Q

what effect does binding on the a2, a3 subunit of the GABAaR have

A

anxiolytic/analgesic

40
Q

what effect does binding on the a5 subunit of the GABAaR have

A

cognition (alzheimers)

41
Q

what effect does binding on the b3 subunit of the GABAaR have

A

immobiloty/anaesthesia

42
Q

what effect does binding on the b2 subunit of the GABAaR have

A

sedation/anaesthesia

43
Q

how quickly does induction of general anaesthethia by progesterone metabolites work

A

rapidly

44
Q

how do progesterone metabolites have such a rapid effect on brain activity

A

non-genomic effect the steroid

45
Q

where do alcohol, antidepressants and GHB exert their effects

A

through neurosteroids

46
Q

what do neurosteriods do

A

fine tune neural inhibition

47
Q

what are strychnine-sensitive glycine receptors

A

anion-selective transmitter-gated ion channels

48
Q

what do strychnine-sensitive glycine receptors regulate

A

respiratory rhythms, motoe control, muscle tone, sensory and pain processing

49
Q

what is the strychnine-sensitive glycine receptor activated by

A

glycine
taurine
strychnine

50
Q

what causes hyperekplexia

A

mutations of the glycine receptor

51
Q

what are the most frequent mutations in the glycine receptor

A

R271L/Q

52
Q

what do mutations of the glycine receptor do

A

decrease both glycine sensitivity and the single channel conductance

biomembranes (9 decks)

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