MSK 16 - Skeletal muscle physiology Flashcards
what does a motor unit consist of
single alpha motor neuron and all the muscle fibres it innervates
if the muscle is for fine control would the alpha motor neuron innervate many or few fibres
few fibres
how many motor units and alpha motor neurons normally supply one muscle
many
the force of contraction is modulated by what factors when considering motor units
modulated by the number and characteristics of motor units recruited
how do muscles within a motor unit contract relative to each other
why is this
in synchrony
excitation in single motor neuron cell causes all muscles it innervates to contract at once
are all muscle fibres within a motor unit the same type
yes
to generate higher force, does the number of motor units recruited need to increase/decrease
increase
skeletal muscle force is graded by recruitment of __ __ with progressively ___ ___ ___
motor units
increasing excitatory input
motor units are normally classified by what
muscle type
what are the two muscle types that a motor unit can be classified as
slow - type 1
fast - type 2
how does the size principle of motor units ensure efficiency
some motor units have different sizes so that they have different properties which creates different resistance to AP propagation and initiation
what order are small and large motor units recruited in
why is this
small oxidative motor units are recruited first as they have a lower threshold
fewer large glycolytic motor units are recruited last
APs are propagated along the alpha motor neurons to reach what
the neuromuscular junction
where does neuromuscular transmission take place
the neuromuscular junction
what must take place in order for muscle motor units to be activated
neuromuscular transmission
what is the structure of the neuromuscular junction both in general of what two structures join together
alpha motor neuron’s terminal bouton synapses with the motor endplate on the muscle fibre
what is the structure of the motor endplate
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
what does the synaptic cleft connect
connection between the synaptic nerve and post synaptic muscle fibre
what is the neurotransmitter that the NMJ
acetylcholine
is the motor endplate part of the presynaptic nerve or post synaptic muscle fibre
its part of the post synaptic muscle fibre
at the NMJ what happens to the myelin sheath
the motor axon loses its myelin sheath at the terminal region of the presynaptic nerve and branches
what cells are the motor neuron nerves covered with and what does this aid in
covered in swann cells - myelin sheaths - that helps the AP propagate along the alpha motor neuron
each branch of the motor axon makes contact with what structure
each branch makes contact with a muscle fibre cell
describe the molecular organisation of the post synaptic folds
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
what are the two Ach R clustering proteins
rapsyn
utrophin
what do the voltage gated Na+ channels do in the depths of the post synaptic membrane
AP is propagated along surface of muscle fibre by voltage gated Na+ channels
what happens at the NMJ in terms of the pre synaptic events - 3 steps starting from AP
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
how do the vesicles release ACh and where do they do this
vesicles membrane fuse with pre synaptic membrane and pumps out the neurotransmitter
do this at the active zone
what are the steps that the vesicles under go in preparation for ACH unloading - 2 things
vesicles filled and form vesicle clusters
filled vesicles dock at active zone and undergo priming ready for Ca2+ triggered fusion pore opening
what happens once the vesicles have unloaded their ACh contents - 3 options
local reuse
fast recycling at the area
clathrin mediated endocytosis and recycling via endosomes where vesicles are filled with ACh
what prevents the presynaptic terminal from enlarging from vesicle binding
vesicles undergo endocytosis and are recycled
AChRs are examples of what kind of channels
directly/ligand gated ion channels
on the post synaptic cells how many subunits are there on the Ach receptor
5 subunits
which of the subunits on the ACh receptor are Ach receptors
the 2 alpha subunits
what opens the channels on the ACh receptor
when receptor has 2 molecules bound the channels open
what happens after the ACh receptor channels open
movement of ions across the membrane causes a current - the end plate current
what two ions are involved in generating the end plate current at the ACh receptor
Na+ and K+
how do Na+ and K+ contribute to the end plate t
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
what happens to the Na+ K+ movement once the end plate current depolarisation has begun
as it depolarises you get less Na+ and K+ movement into region as the conc gradient is decreasing
what are the post synaptic events at the NMJ - 4 things
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
the end plate current and end plate potential are terminated by what and how does this happen
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
where is the enzyme Achetylcholinesterase located
what structures does it hold together
anchored to the collagen fibrils of the basement membranes
holds the presynaptic nerve and muscle end plate together
what does AchE do to ACh
hydrolyses it
ACh + H2O -> choline and acetate
what happens to the components of ACh after its been hydrolyzed by AChE
choline diffuses back into the presynaptic terminal and is reabsorbed and loaded back into vesicles
AChE is the physiological target of which substances
insecticides and military nerve gases
what are the two types of neurological blockades which are used during surgery
depolarising
non-depolarising
depolarising neurological blockades have what sort of a relationship with AChR and AChE
AChR agonist
not broken down by ACh-esterase
Non depolarising neurological blockades have what sort of a relationship with AChR and channels
AChR antagonist
binds but doesnt open channels
what do agonists do and what do antagonists do to receptors
agonists = activate receptor and allows for intracellular response
antagonist = blocks receptors and prevents process and response
what are alpha toxins
specific blockers of nicotinic AChRs
what is the specific type of channel are the AChRs at the post synaptic cell
nicotinic ACh-gated ion channel
the end plate current causes a change in what
in membrane potential
the current increases above threshold and what event follows
AP is automatically fired
what happens to the end plate current when a alpha toxin is applied
the membrane potential does not exceed threshold - thus the AP is not fired
the end plate potential is always ____ in vivo
supra-threshold
how far can end plate potentials travel
why is this
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
what is the duration of end plate potential determined by
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
what are 3 examples of abnormal pre-synaptic transmissions
lambert eaten syndrome
diabetes
naturally occuring toxins like botox
what are 4 examples of abnormal post-synaptic transmissions
alpha toxins
anti-AChE
organophosphates that prevent AChE breakdown
depolarising (ACh agonists) or non depolarizing drugs (ACh Antagonists)
do alpha toxins affect the pre or post synaptic neuromuscular transmission
post
what is the most common primary disorder of the NMT
myasthenia gravis
what is myasthenia gravis and what are its symptoms
autoimmune disease resulting in fewer AChRs
causes weakness and fatigability of voluntary muscles especially facial muscles
how can myasthenia gravis be treated (to some extent)
how does this work
AChE inhibitors which would prolong the activity of ACh at the NMJ
what is the consequence of having fewer AChRs due to myasthenia gravis
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