NTs 3

Question 1

major inhibitory NT is? charged? other inhibitory NT?

Answer 1

GABA. neutral. other inhibitory NT = glycine, also neutral

Question 2

GABA dysfunction associated with? drugs?

Answer 2

epilepsy, Huntington’s disease, tardive dyskinesia, alcoholism, sleep disorders. anticonvulsant, anti-anxiety and sedative drugs enhance GABA function

Question 3

neutral amino acid NTs: main mechanism?

Answer 3

increase Cl- permeability. IPSPs.

Question 4

chloride movement at RMP?

Answer 4

RMP = - 60 mV which is less than ECl. so Cl comes in, and you get an EPSP. influx down concentration gradient more important than electrical gradient

Question 5

Cl- movement at -110 mV?

Answer 5

Em = -110 mV which is greater than ECl. Cl leaves cell = reversed IPSP, since electrical gradient larger

Question 6

reversal potential for Cl-

Answer 6

-80 mV. when Em = ECl so chemical gradient and electrical gradient is balanced, no net movement of Cl-. stimulation of channels won’t alter membrane potential

Question 7

current voltage relationship of IPSP: what it looks like at different membrane potentials

Answer 7

strongly depolarized = large IPSP. RMP = normal IPSP. -80 mV aka reversal/equilibrium potential: flat line. strongly hyperpolarized: reversed IPSP now Cl is leaving the cell

Question 8

where is GABA made and broken down

Answer 8

GABA made in neurons. then transported into astrocytes where it is broken down

Question 9

GABA synthesis: how?

Answer 9

glutamate, glutamaic acid decarboxylase GAD converts it into GABA

Question 10

marker for GABA neurons

Answer 10

GAD: glutamic acid decarboxylase which converts glutamate to GABA

Question 11

GABA breakdown: where and how

Answer 11

in astrocytes, with GABA-T (gaba transmiaminase. at the same time it breaks GABA down, it transfers amino group to a-ketoglutarate to make glutamate

Question 12

breakdown of GABA by ____ provides?

Answer 12

by GABA-T: provides NH2 for synthesis of glutamate

Question 13

after GABA is made: transported into? how?

Answer 13

transported into vesicles with a transporter that depends on electrical potential across vesicular membrane

Question 14

released GABA: then what happens?

Answer 14

taken up and recycled via Na/Cl dependent transporter. also taken up into glia and metabolised by GABA-T to succinic semialdehyde while a-ketoglutarate is made into glutamate

Question 15

glutamaic acid decarboxylase not present where? present where? so implication?

Answer 15

not found in glia, only in neurons. so released glutamate is taken back into neurons where it is converted into GABA.

Question 16

GABA-T involved in?

Answer 16

synthesis and metabolism of GABA

Question 17

GABA-A receptors: structures

Answer 17

similar to nAChR: give subunits each with different gene products. each subunit has 4 TM domains.

Question 18

AAA vs. IAA structure

Answer 18

acidic/excitatory AA receptors: 4 subunits with 3 TM domains. inhibitory AA receptors: 5 subunits X 4 TM domains

Question 19

GABA-A receptors: site of action for what drugs

Answer 19

anxiolytic benzodiazephines, sedatie and hypnotic drugs like barbiturates and ethanol

Question 20

bicuculline

Answer 20

selective GABA-A receptor antagonist, convulsant

Question 21

GABAZINE

Answer 21

GABA-A antagonist, aka SR 95531

Question 22

picrotoxin

Answer 22

blocks Cl channel of GABA A receptor, is a convulsant

Question 23

synaptic vs. extrasynpatic GABA-A receptors: subunits

Answer 23

synaptic GABA - A receptor most abundant isoform is a1b2y2. important is having a1. extrasyanptic found further away, a4b3d

Question 24

extrasynaptic GABA-A receptors: sensitizing? location? what type of inhibition

Answer 24

slowly desensitize, located away from cleft, may be tonically activated by ambient GABA levels = tonic not phasic synpatic inhibition.

Question 25

GABA-B receptor: structure? coupled to?

Answer 25

metabotropic, 7 TM and usually form dimers. couple to Gi in pre/post synpatic membranes

Question 26

GABA-B mechanism of action post synpatically

Answer 26

open G protein coupled inwardly rectifying K+ channels aka GIRK channels = post synpatic hyperpolarization and inhibition

Question 27

baclofen

Answer 27

GABA-B selective agonist = muscle relaxant

Question 28

GABA-B mechanism presynpatically

Answer 28

close presynpatic Ca channels = decreased transmitter release. can also be found presynpatically on glutamate terminals

Question 29

glycine: synthesis where and how

Answer 29

L -serine to glycine via serine hydroxymethyltransferase. in neurons.

Question 30

glycine breakdown: where and how

Answer 30

glycine taken up into astrocytes via Na/Cl dependent transporty GLYT1/2 into astrocytes. glycine cleavage system breaks it down to CO2 and NH2

Question 31

glycine receptors: type? structure?

Answer 31

ionotrpic only. pentameric receptors, composed of a and b subunits

Question 32

strychnine

Answer 32

painful convulsant, classical glycine antagonist