Unit 7: skeletal muscle Flashcards
the vast majority of skeletal muscles have cells that are innervated by this many motor neurons
ONE
where do the motor neuron cell bodies lie in the spinal cord?
the ventral (anterior) horns
what are two pathways for motor neurons to get “excited”?
- the descending pathways from the brain
- the reflex arcs
what is the sarcoplasmic reticulum (SR)?
where skeletal muscle stores Ca2+
what are the transverse (T) - tubules
these tubules helps propogate the AP across the muscle fibers
what are the two contraction elements in a skeletal muscle fiber?
actin + myosin
these structures shorten the muscle fibers during contraction
what is the mitochondria’s role in the skeletal muscle?
helps provide ATP to the skeletal muscle
also located in presynaptic neuron for ATP use in ion channels
provides “acetate” for ACh formation
differentiate primary vs secondary clefts
primary: one infolding
secondary: two infoldings within one groove
Where are the ACh receptors located on the subneural clefts?
typically on the more superior/surface of the subneural cleft
where do VG Na+ channels lie in the subneural cleft?
they are congregated deeper inside the cleft at the base and along the inferior walls
what is AChE?
an enzyme that breaks down ACh
expressed by the skeletal muscle and parks it in the NMJ
it shuts the stimulus (ACh) down to allow neuronal repolarization
how does AChE break down ACh?
hydrolysis to form acetyl/acetate and choline
choline can be recycled into the neuron
how many ACh-Rs are at a typical NMJ?
5 million
how many ACh-Rs get activated at a typical NMJ during AP?
500,000 or 10% of 5 million
how many ACh molecules typically get released into the NMJ during an AP?
1 million at bare minimum (to elicit muscle contraction)
typically 2 million, but not all the ACh makes it to the skeletal muscle (d/t AChE)
on a N-ACh-R, which subunit binds the ACh molecules?
the alpha subunits bind the 2 ACh molecules
what is an example of a n-ACh-R antagonist?
curare
curare can bind to ___ subunit on the n-ACh-R to shut it down
ONE
(does not need to bind to both alpha subunits)
this sets up exocytosis for ACh release into NMJ
Ca2+
what are the voltage sensors in a skeletal muscle cell and what do they do?
voltage sensors located in the t-tubules & cellular wall recognize an AP that is propogated by the fast Na+ channels
these voltage sensors are AKA dihydropyridine (DHP) receptors
in response to an AP, DHPRs will “tug” on their attachment to the calcium release channels to liberate Ca2+ “popping the cork”
SOME Ca2+ can influx via the dihydropyridine receptors (but not much)
what is a RyR (ryanodine receptor)?
RyR is a Ca2+ release channel gatekeeping Ca2+ in the SR
what is SERCA?
“sarcoplasmic endoplasmic reticulum calcium ATPase”
this structure burns ATP to put Ca2+ BACK into the SR against it’s [ ] gradient
list all the steps to excitation-contraction coupling:
- motor neuron depolarizes from brain/or reflex arcs
- Ca2+ influx to motor neuron – primarily thru voltage sensitive p-type Ca2+ channels
- ACh storage vesicles fuse to presynaptic neural cell wall/membrane
- ACh released into NMJ via exocytosis
- 2 ACh bind to 1 n-ACh-R; primarily sodium INFLUX and secondarily Ca2+ influx
- threshold potential met generating EPP/local depol and (as long as skeletal tissue is healthy) turns into an AP
- AP spreads down muscle fibers in bidirectionally
- AP spreads via VG Na+ channels
- muscle depolarization sensed by DHPRs (in t-tubules and cell wall)
- DHPRs pull on RYR “doors” to release Ca2+ from SR
- Ca2+ influx into sarcoplasm; recycled into SR via SERCA
- Ca2+ removed from sarcoplasm terminates contraction
how does Ch get recycled back into presynaptic neuron?
- Ch pump (ATP)
- Ch/Na+ co-transporter
what structure is located in cell wall to store Ch for later use?
phosphatidylcholine
there are more leaky Na+ channels on a neuron than leaky K+ channels: true or false
false
leaky K+ ch > leaky Na+ ch
describe how myasthenia gravis affects skeletal muscle
MG is an autoimmune disorder where the body produces antibodies to target n-ACh-Rs; usually due to an abnormal thymus gland
if plenty of Ab get destroyed by immune system, there is less surface area for n-ACh-Rs (covered by scar tissue; usually in the clefts) and less fast Na+ channels
this would lead to impaired ability to conduct AP > leads to progressive neuromuscular dysfunction
the disease gets worse throughout the day
what are the treatments to MG?
- thymectomy
- plasmapherisis (filter out Abs)
- NMJ drugs
+drugs that target AChE (AChE-inhibitors)//”-stigmine” drugs
how would “-stigmine” drugs help MG patients?
by inhibiting the degradation of ACh in the synapse, this allows more ACh to interact with n-ACh-Rs; this will increase the overall probability to open the receptors
what is LEMS/ELMS?
“lambert-eaton myasthenic syndrome”
a paraneoplastic syndrome that develops in CA patients
involves Abs against P-type Ca2+ channels; this results in a Ca2+ deficiency in the motor neuron
what are some treatments for LEMS/ELMS patients?
- plasmapheresis
- remove the cancerous tumor
- K+ channel blockers
+depolarization will be enhanced; depolarization will be longer and repolarization will become SLOWER
this increases the opportunity of p-type Ca2+ channels opening for Ca2+ release
why don’t AChE-Is work for LEMS patients?
AChE-Is will prevent ACh from getting broken down; with the P-type Ca2+ channels being targeted, there is a Ca2+ deficiency and Ca2+ is needed to release ACh from the synapse
therefore if there is no Ca2+ to be released, there is no ACh in the synapse
what are some examples of K+ channel blockers?
- TEA - tetraetyhlammonium
- 4,5-diaminopyrimidine
these drugs are very dangeous as they are non-specific to K+ channels
(unlike amiodarone – amio is a poor K+ channel blocker)
describe a non-depolarizing paralytic
curare is a non-depolarizing NMBA
it binds to the alpha subunit of the n-ACh-R which will cause the skeletal muscle to relax and prevents AP from occuring
describe an give an example of a depolarizing paralytic
succinylcholine (sux)
a depolarizing paralytic means that the succinylcholine molecule will bind to n-ACh-R, and keep the receptors OPEN
if the receptor is open for a prolonged period of time, this causes a sustained depolarization
initially fasiculations occur, then repolarization is prolonged d/t a sustained AP d/t Na+ influx and VG Na+ channels will close their H gates to remain in their inactive state
if all VG Na+ channels are in inactive state, the channels cannot open the activation gate and will NOT produce new APs
why does sux not get broken down by AChE?
sux is not broken down by AChE – sux is 2 ACh molecules joined at the acetyl groups and AChE has a hard time breaking the ester bonds
describe how sux can cause a potassium leak
K+ leak channels don’t ever close; but the K+ channels will start to efflux d/t prolonged depolarization and membrane potential will become more positive for a prolonged period of time
this will allow K+ to efflux thru the leaky K+ channels to flow across the electrochemical gradient
by how much does sux raise ECF K+ levels in a healthy person? in a person with skeletal muscular issues?
in a normal person: 0.5
in someone who might have skeletal muscle issues: hyperkalemia
why would a CVA patient be at risk for hyperkalemia if given sux?
CVA patients have acute neuromuscular issues which can cause denervation
if they are not using their muscles as often there will be an increase in n-ACh-Rs that are not confined to just the NMJ
if sux is given, potassium leak channels will also leak throughout areas not confined to the NMJ and will cause hyperkalemia
