MSK 16 - Skeletal muscle physiology

Question 1

what does a motor unit consist of

Answer 1

single alpha motor neuron and all the muscle fibres it innervates

Question 2

if the muscle is for fine control would the alpha motor neuron innervate many or few fibres

Answer 2

few fibres

Question 3

how many motor units and alpha motor neurons normally supply one muscle

Answer 3

many

Question 4

the force of contraction is modulated by what factors when considering motor units

Answer 4

modulated by the number and characteristics of motor units recruited

Question 5

how do muscles within a motor unit contract relative to each other

why is this

Answer 5

in synchrony

excitation in single motor neuron cell causes all muscles it innervates to contract at once

Question 6

are all muscle fibres within a motor unit the same type

Answer 6

yes

Question 7

to generate higher force, does the number of motor units recruited need to increase/decrease

Answer 7

increase

Question 8

skeletal muscle force is graded by recruitment of __ __ with progressively ___ ___ ___

Answer 8

motor units

increasing excitatory input

Question 9

motor units are normally classified by what

Answer 9

muscle type

Question 10

what are the two muscle types that a motor unit can be classified as

Answer 10

slow - type 1
fast - type 2

Question 11

how does the size principle of motor units ensure efficiency

Answer 11

some motor units have different sizes so that they have different properties which creates different resistance to AP propagation and initiation

Question 12

what order are small and large motor units recruited in

why is this

Answer 12

small oxidative motor units are recruited first as they have a lower threshold

fewer large glycolytic motor units are recruited last

Question 13

APs are propagated along the alpha motor neurons to reach what

Answer 13

the neuromuscular junction

Question 14

where does neuromuscular transmission take place

Answer 14

the neuromuscular junction

Question 15

what must take place in order for muscle motor units to be activated

Answer 15

neuromuscular transmission

Question 16

what is the structure of the neuromuscular junction both in general of what two structures join together

Answer 16

alpha motor neuron’s terminal bouton synapses with the motor endplate on the muscle fibre

Question 17

what is the structure of the motor endplate

Answer 17

there is an active zone where there are vesicles filled with acetylcholine and below it is the synaptic cleft

below the synaptic cleft there are clefts in the muscular endplate with acetylcholine receptors at the top

Question 18

what does the synaptic cleft connect

Answer 18

connection between the synaptic nerve and post synaptic muscle fibre

Question 19

what is the neurotransmitter that the NMJ

Answer 19

acetylcholine

Question 20

is the motor endplate part of the presynaptic nerve or post synaptic muscle fibre

Answer 20

its part of the post synaptic muscle fibre

Question 21

at the NMJ what happens to the myelin sheath

Answer 21

the motor axon loses its myelin sheath at the terminal region of the presynaptic nerve and branches

Question 22

what cells are the motor neuron nerves covered with and what does this aid in

Answer 22

covered in swann cells - myelin sheaths - that helps the AP propagate along the alpha motor neuron

Question 23

each branch of the motor axon makes contact with what structure

Answer 23

each branch makes contact with a muscle fibre cell

Question 24

describe the molecular organisation of the post synaptic folds

Answer 24

two distinct domains

crests (close to the motor end plate) = high conc of Ach receptors and Ach receptor clustering proteins rapsyn and utrophin

depths (far from the motor end plate) = high conc of voltage gated Na+ channels

Question 25

what are the two Ach R clustering proteins

Answer 25

rapsyn utrophin

Question 26

what do the voltage gated Na+ channels do in the depths of the post synaptic membrane

Answer 26

AP is propagated along surface of muscle fibre by voltage gated Na+ channels

Question 27

what happens at the NMJ in terms of the pre synaptic events - 3 steps starting from AP

Answer 27

AP in presynaptic cell reaches nerve terminal depolarization opens voltage gated Ca2+ channels leading to Ca2+ influx increased Ca2+ conc triggers exocytosis of vesicles and release of ACh from vesicles into the synaptic cleft

Question 28

how do the vesicles release ACh and where do they do this

Answer 28

vesicles membrane fuse with pre synaptic membrane and pumps out the neurotransmitter do this at the active zone

Question 29

what are the steps that the vesicles under go in preparation for ACH unloading - 2 things

Answer 29

vesicles filled and form vesicle clusters filled vesicles dock at active zone and undergo priming ready for Ca2+ triggered fusion pore opening

Question 30

what happens once the vesicles have unloaded their ACh contents - 3 options

Answer 30

local reuse fast recycling at the area clathrin mediated endocytosis and recycling via endosomes where vesicles are filled with ACh

Question 31

what prevents the presynaptic terminal from enlarging from vesicle binding

Answer 31

vesicles undergo endocytosis and are recycled

Question 32

AChRs are examples of what kind of channels

Answer 32

directly/ligand gated ion channels

Question 33

on the post synaptic cells how many subunits are there on the Ach receptor

Answer 33

5 subunits

Question 34

which of the subunits on the ACh receptor are Ach receptors

Answer 34

the 2 alpha subunits

Question 35

what opens the channels on the ACh receptor

Answer 35

when receptor has 2 molecules bound the channels open

Question 36

what happens after the ACh receptor channels open

Answer 36

movement of ions across the membrane causes a current - the end plate current

Question 37

what two ions are involved in generating the end plate current at the ACh receptor

Answer 37

Na+ and K+

Question 38

how do Na+ and K+ contribute to the end plate t

Answer 38

Na+ is high conc in extracellular fluid and low in intracellular fluid (cytosol of muscle fibres) K+ is high conc in intracellular fluid and low in extracellular fluid when channels on AChR opens both Na+ and K+ move down their concentration gradient and depolarises the region

Question 39

what happens to the Na+ K+ movement once the end plate current depolarisation has begun

Answer 39

as it depolarises you get less Na+ and K+ movement into region as the conc gradient is decreasing

Question 40

what are the post synaptic events at the NMJ - 4 things

Answer 40

2ACh binds at transmitter gated channels channel opens leading to Na+ inflow and K+ outflow motor end plate is locally depolarised by current voltage gated Na+ channels open causing Na+ inflow which depolarises the area and propagates muscle AP

Question 41

the end plate current and end plate potential are terminated by what and how does this happen

Answer 41

terminated by ACh-esterase in the synaptic cleft does so by creating unbinding of Ach at the AChR binding which reduces ACh concentration in the synaptic cleft

Question 42

where is the enzyme Achetylcholinesterase located what structures does it hold together

Answer 42

anchored to the collagen fibrils of the basement membranes holds the presynaptic nerve and muscle end plate together

Question 43

what does AchE do to ACh

Answer 43

hydrolyses it ACh + H2O -> choline and acetate

Question 44

what happens to the components of ACh after its been hydrolyzed by AChE

Answer 44

choline diffuses back into the presynaptic terminal and is reabsorbed and loaded back into vesicles

Question 45

AChE is the physiological target of which substances

Answer 45

insecticides and military nerve gases

Question 46

what are the two types of neurological blockades which are used during surgery

Answer 46

depolarising non-depolarising

Question 47

depolarising neurological blockades have what sort of a relationship with AChR and AChE

Answer 47

AChR agonist not broken down by ACh-esterase

Question 48

Non depolarising neurological blockades have what sort of a relationship with AChR and channels

Answer 48

AChR antagonist binds but doesnt open channels

Question 49

what do agonists do and what do antagonists do to receptors

Answer 49

agonists = activate receptor and allows for intracellular response antagonist = blocks receptors and prevents process and response

Question 50

what are alpha toxins

Answer 50

specific blockers of nicotinic AChRs

Question 51

what is the specific type of channel are the AChRs at the post synaptic cell

Answer 51

nicotinic ACh-gated ion channel

Question 52

the end plate current causes a change in what

Answer 52

in membrane potential

Question 53

the current increases above threshold and what event follows

Answer 53

AP is automatically fired

Question 54

what happens to the end plate current when a alpha toxin is applied

Answer 54

the membrane potential does not exceed threshold - thus the AP is not fired

Question 55

the end plate potential is always ____ in vivo

Answer 55

supra-threshold

Question 56

how far can end plate potentials travel why is this

Answer 56

short distances EPPs arent propagated like nerve/muscle APs, they are just localised change of potential due to ACh only being in that one place on the muscle fibre

Question 57

what is the duration of end plate potential determined by

Answer 57

the mean open time of all AChRs at the synapse ie how long the AChRs stay open which in turn is determined by the AChE activity

Question 58

what are 3 examples of abnormal pre-synaptic transmissions

Answer 58

lambert eaten syndrome diabetes naturally occuring toxins like botox

Question 59

what are 4 examples of abnormal post-synaptic transmissions

Answer 59

alpha toxins anti-AChE organophosphates that prevent AChE breakdown depolarising (ACh agonists) or non depolarizing drugs (ACh Antagonists)

Question 60

do alpha toxins affect the pre or post synaptic neuromuscular transmission

Answer 60

post

Question 61

what is the most common primary disorder of the NMT

Answer 61

myasthenia gravis

Question 62

what is myasthenia gravis and what are its symptoms

Answer 62

autoimmune disease resulting in fewer AChRs causes weakness and fatigability of voluntary muscles especially facial muscles

Question 63

how can myasthenia gravis be treated (to some extent) how does this work

Answer 63

AChE inhibitors which would prolong the activity of ACh at the NMJ

Question 64

what is the consequence of having fewer AChRs due to myasthenia gravis

Answer 64

may not get every AP in the nerve depolarising motor end plate regions sufficiently to open the voltage gated Na+ channels on the post synaptic membrane