Ligand-gated Rs

Question 1

What are the 2 types of ACh?

Answer 1

Nicotinic

Muscarinic

Question 2

What does nACh bind to?

What does mAch bind to?

Answer 2

nACh = Ligand-gated channels

mACh = G-protein coupled Rs

Question 3

What is a nAChR composed of?

Answer 3

5 SUBUNITS

(i.e. alpha, beta, gamma etc.)

Each subunit has 4 DOMAINS! :

(M1, M2, M3 and M4)

-CHANNEL IS LINED BY M2 DOMAIN!

Question 4

What lines the nACH R channel?

Answer 4

M2 DOMAIN! (of each subunit)

Question 5

What happens when a nACh-R is opened?

Answer 5

TWISTING of transmembrane domains lining pore

-exposes polar a.a residues!

Question 6

How did scientists discover that M2 lines the nACh-R pore?

Answer 6

CHIMERIC study!

Question 7

What ions are favoured to enter cell thru ligand-gated channels?

Answer 7

ligand-gated channels (a.k.a nACHR)

-have (-) charged rings (in pore vestibules)

THUS, CATIONS (+) thru!

Question 8

What occurs in MUSCLE nACh-Rs from EMBRYOS to ADULTS?

Answer 8

SUBUNIT COMPOSITION CHANGE!

(gamma to epsilon)

THUS, channels stay OPEN LONGER IN EMBRYONIC nACHR!

Question 9

WHERE are the nACh-Rs expressed on muscle cells in both embryos and adults?

Answer 9

EMBRYOS = extrajunctional

(spread over the muscle cell)

ADULT = junctional

(tightly clustered @ ENDPLATE!)

Question 10

Discuss nACh-Rs in EMBRYOS

Answer 10

Long open times

&

Broad R distribution

-allows initial establishment of synaptic connections

Question 11

Discuss nACh-Rs in their mature state (ADULTS)

Answer 11

Shorter open times

&

Less R distribution

-allows precise & rapid signalling in the neuromuscular junction (fast use of muscle)

Question 12

What does competition for synapses lead to?

Answer 12

Synapse elimination from certain axons

Question 13

What are the members of the Cys-loop ionotropic superfamily Rs?

Answer 13

ACh

GABA

Glycine

Question 14

What do the Cys-loop ionotropic superfamily Rs have in common?

Answer 14

They all have CYSTEINE RESIDUES

Question 15

What is the function of cysteine residues in cys-loop ionotropic superfamily Rs?

Answer 15

Form COVALENT BONDS (disulfide bridges)

THUS, stabilise the 3D structure!

NOTE: it’s these covalent bonds the limit the TWISTING when pore is opened!!

Question 16

What are the two types of GABA Rs?

Answer 16

–Direct ligand-g (GABA a)

(5 subunit, M2 pore, cys-loop)

–G-protein c. Rs (GABA b)

Question 17

Ionotropic Rs = ?

Answer 17

Ligand-gated Rs

Question 18

Metabotropic Rs = ?

Answer 18

G-protein coupled Rs

Question 19

What class of R is part of a different distinct family (other that cys-loop.)?

Answer 19

Ionotropic GLUTAMATE Rs!

Question 20

What classes are ionotropic glutamate Rs divided into?

Answer 20

NMDA

&

non-NMDA

Question 21

What ligand(s) bind with iGluRs?

Answer 21

[iGluRs = NMDA & non-NMDA (ionotropic)]

–GLUTAMATE is the native ligand!
BUT, can also come in different forms:

–AMPA

(GluR 1-4)

& kainate

(GluR 5-7)

–NMDA

(NR1, NR2, NR3)