Topic 3:3

Question 1

Alpha motor neurons

Answer 1

fast control of skeletal muscles
large myelinated Aa nerves
from spinal cord/brainstem to neuromuscular junction on muscle

Question 2

motor unit

Answer 2

a single motor neuron and the group of muscle fibres it innervates

Question 3

motor end plate

Answer 3

at the neuromuscular joint, the nerve fibres connect to special sites on the muscle’s membrane called motor end plate

Question 4

ACh is a

Answer 4

NP transmitter

Question 5

Life cycle of ACh

Answer 5

precursor acetyl coenzyme A produced in mitochondria
released into cytoplasm of the terminal, and then produces ACh which is stored in vesicles
Packaging involves an antipode ion pumps that exchanges H+ from within vesicle for ACh molecules in cytoplasm
fusion with membrane releases ACh into syanpse
broken down by an enzyme that is also present on post synaptic end plate membrane to release acetate and choline

Question 6

choline reabsorbed by presynaptic terminal

Answer 6

using Na+ exchange pump as it is an essential nutrient

Question 7

depolarisation of motor neuron terminal

Answer 7

has no voltage gated Na+ channels so cant produce AP
Depolarisation caused by influx of Ca++ (depolarisation from prior AP’s electrotonic current flow opens voltage gated Ca++ channels)

Question 8

Intracellular sources of Ca++

Answer 8

depolarisation of terminal activates a GPCR, activates phosphoinositol-Phospholipase C to cause release of IP3 from intracellular stores
IP3 play major role in releasing Ca++ from ER

Question 9

Proteins involved in vesicle fusion

Answer 9

synaptogamin and synaptobrevin on vesicle membrane
SNARE proteins (SNAP-25 and Syntaxin) on terminal membrane
attacked by neurotoxins

Question 10

neurotoxins

Answer 10

attack proteins involved in vesicle docking to prevent vesicles from fusing with membrane and releasing their ACh to activate the underlying muscle

Question 11

clathrin-mediated endocytosis

Answer 11

dominant mechanism for recycling during low or mild neuronal activity
vesicle membrane tagged from rest of terminal membrane
all proteins in vesicle membrane extruded leaving only lipid bilayer of membrane
membrane coated with clathrin
pinched off from membrane and number of triskelia assemble into hexagon or pentagon lattice

Question 12

3 main processes of clathrin mediated endocytosis

Answer 12

demarcating the vesicle membrane from the terminal membrane by coating it
pinching it off from the terminal membrane using energy from GTP
Closing off the vesicle membrane for internalisation and reuse

Question 13

unlike exocytosis, endocytosis

Answer 13

takes place away from the active zone

Question 14

ACh released from motor neuron terminal and diffused across cleft has 4 potential fates

Answer 14

binds to receptors for it on end plate
bind to an enzyme on endplate or in synapse that destroys it
diffuse away
reuptake by nerve terminal

Question 15

nAChR

Answer 15

ionotropic

opening/closing directly modulates flow of ions to produce rapid changes in the post synaptic MP

Question 16

mAChR

Answer 16

metabotropic

GPCRs

Question 17

muscle end plate nAChR

Answer 17

two ACh can bind to the two alpha subunits
allows flow of cations
Na+ and Ca+ move in via conc gradient while K+ moves out

Question 18

AChR 3 states

Answer 18

resting (channel closed)
resting with agonist (ACh bound but channel closed)
active with agonist (ACh bound and channel open)

Question 19

Muscle RMP

Answer 19

-80mV

Question 20

End plate potential

Answer 20

opening channels means more Na+ movement than K+
net influx of positive charge causes depolarisation called EPP
Size related to amount of ACh that binds to post synaptic AChRs
Size of EPP is so large to start with that, despite leakage as the current flows along, the muscle will produce an AP
longer presence of Ca++ makes depolarisation longer

Question 21

ACh esterase

Answer 21

end plate trough reduces diffusion away and there are no glial cells for reuptake so only an enzyme can terminate
AChE in synapse and end plate membrane break down ACh into acetic acid and choline
choline reabsorbed by presynaptic terminal using a choline transporter and combined with acetic acid to form more acetyl choline, which enters synaptic vesicles

Question 22

Key features of transmission at NMJ

Answer 22

always excitatory
one to one
fail safe

Question 23

Factors that can cause failure at NMJ

Answer 23

ACh release inhibitors
AChR inhibitors
AChE inhibitors

Question 24

Myasthenia Gravis

Answer 24

antibodies block ACh receptors
IgG antibodies present at NMJ ross link AChRs, cluster them and endocytose
Also block AChRs so that ACh cant bind so instead are broken down by AChE

Question 25

smaller EPP results from

Answer 25

fewer interactions between ACh and receptors
‘safety factor’ is reduced, less chance of AP
less chance of muscle contraction

Question 26

ACh rundown results from

Answer 26

repeated nerve activation

MG: decreases of receptors in myasthenia junctions