Lecture 12; 9/23 - Skeletal Muscle Flashcards
Test 2
The skeletal muscle is the larget contributer to body ________ and _______ in non obese people
weight
volume
How does the sketel muscle help regulate body temperature?
The vast amount of muscle acts as insulation to keep heat in
Thermoregulation: which includes shivering which is small muscle contractions
Where are the motor neuron cell bodies located?
Anterior or ventral horn of grey matter in the spinal cord
What can motor neurons be activated by?
The descending pathways in the white matter from the brain
or the reflex arc which includes sensory information coming in from the dorsal horns
How many motor neurons are most skeletal muscles controlled by?
One
Describe the reflex arc
Feeds in through the dorsal horn in the grey matter in the spinal cord to excite the motor neuron cell body. The movements produced from the reflex arc are rapid and involuntary
What muscle is controlled by multiple motor neurons?
Ocular Muscle
_____ and cells are interchangeable terms
fibers
Can motor neurons control more than 1 muscle fiber?
True
What is the Neuromuscular junction?
NMJ
Where motor neuron comes in contact with the skeletal muscle
What is the shape of skeletal muscle fibers?
Long, thick, wide cylinders
What does the motor unit consist of?
Motor axon ad NMJ
What are the contractile proteins? and where are they located?
Actin and Myosin
Inside the skeletal muscle fibers
What does sacro mean?
Muscle
What is the Sacroplasmic reticulum?
SR
Overdeveloped endoplasmic reticulum for SPECIFICALLY for skeletal muscle cells.
Stores Ca++ for internal use for contractions
What is the nickname for the transverse tubules?
T-tubules
What is a transverse tubule?
perpendicular tube or enfolding that allows the AP to carry and spread to penetrate and activate deep into the muscle
What happens during a contraction?
Actin/Myosin (Muscle) shortens
T/F: One motor neuron can connect to several skeletal muscle cells
T
T/F: You can only have one motor neuron per muscle fiber?
F
Large muscles can have several
What is Acetylcholinesterase?
Enzyme that uses HYDROLYSIS to breaks down Acetylcholine to Acetate and Choline to help shut down the signaling at the nAch receptor to prep for another AP
Limits depolarization
Where is Acetylcholinesterase made and located?
It is made in the skeletal muscle
It is fastened to the skeletal muscle at the NMJ near the clefts/nAch receptors
Where are the nAch receptors located on the skeletal muscles?
At the NMJ inside the clefts but towards the surface of the clefts.
What are clefts?
Located at the NMJ
Little pits on the skeletal muscle that contain nAch receptor and V-G Na+ channels
Motor neurons are wrapped in ______ which is maintained by _________ cells
Myelin
Schwann
What are secondary clefts?
A cleft that has 2 pits in 1
Where are Schwann cells located?
The terminal end of the motor neuron (the end closes to the NMJ)
How many nAch receptors at a NMJ?
5 million
How many nAch receptos are activated during a typical synaptic response?
500,000 which is about 10%
How many Acetylcholine molecules need to be released during an AP? How many are actually released?
About 1 million
About 2 million because 1/2 of them don’t bind to a receptor (acetylcholinesterase degrades them before reaching receptor)
How many subunits are on a nAch receptor?
5
What subunits need binding on the nAch receptors to activate it?
Both Alpha subunits
Explain the flow of ions when a nAch receptor is activated through that receptor.
Na+ floods into the cell
A small amount of Ca++ comes in but it’s large so it does go through the receptor well
An even smaller amount of K+ leaves through here. Large Ca++ is in the way
What happens to K+ during the activation of a nAch receptor?
A small amount will leave out via the receptor. But since the cell is being depolarized, it will be so positive that it will want to push K out of the K+ leak channels.
What naturally occuring paralytic are most of our non-depolarizing paralytics modeled after?
Curare
What are non-depolarizing paralytics?
nAch Antagonists
nAch receptor antagonists need to block ___ binding site(s).
1
What sets up exocytosis?
Calcium
What happens with exocytosis at the NMJ?
- Ca++ brought in to the pre-synapse by the P-type Ca++ transporter
- Acetylcholine storage vessicle brought towards the cell wall
- Acetylcholine storage vessicle fuses with the cell wall
- Acetylcholine released into the NMJ
What does DHP mean?
Dihydropyridine
How does an AP spread in 2 words?
Outward; deep/down
How is the AP able to spread downward?
Transverse tubules
What are in the transverse tubules?
Fast Na+ channels
Where is the Sacroplasmic reticulum located?
Near the skeletal cell wall, T-tubules, and the DHP receptors (Voltage sensors)
What is attached to the sarcoplasmic reticulum?
A Ca++ release channel
Describe the Ca++ release channel on the SR?
It’s triggered by the DHP receptor/voltage sensors in which when they sense an AP they spring the top of the Ca++ release channel open so Ca++ can flood into the cell and the muscle can contract
What is a DHP receptor?
“Voltage Sensor”
Dihygropyridine receptor detects an AP and and opens up the Ca++ release channels
Where are the DHP voltage sensors located?
In the T tubulues and the cell wall
T/F: Ca++ flows out of the DHP receptor.
T
Such a very small amount though.
This is NOT a real receptor
What does the DHP receptor mimic?
A V-G Ca++ channel BUT DO NOT GET IT CONFUSED IT IS NOTTTTTTTT
What does SERCA mean?
Sacroplasmic Endoplasmic Reticulum Ca++ ATPase
What does the SERCA pump do?
Uses ATP to pump Ca++ against its concentration gradient back into the SR after an AP.
What is another name for the Ca++ Release channels and why?
Ryanodine Receptor
The channel will open to Ryanodine
What causes a contraction?
An AP causes a trigger in the DHP voltage sensor which opens the Ca++ release channel to allow Ca++ to flood into the cell causing a contraction in actin/myosin
What do dihydropyridine Ca++ channel blockers do?
They block the activity at the DHP voltage sensor to prevent Ca++ from being released into the skeletal muscle cells
Describe the sequence of events of Excitation-Contraction Coupling:
- Signaling to the motor neuron from the brain or reflex arc and if strong enough will generate AP
- Motor neuron depolarizes
- P-type activated; Ca++ floods into presynapse
- Acetylcholine vessicles move towards the cell
- Exocytosis happens and Ach is excreted into the NMJ
- 2 Ach binds with a nAch receptor which activates it; Na+ and Ca+ come in and a small amount of K+ comes out.
Local Na+ and Ca++ influx generates End plate potential which in healthy tissues will always generate an AP
- The flooding of Na+ into the skeletal muscle generates an AP by activating the VG-Na+ channels and fast Na+ channels (skeletal muscle depolarized)
- AP is spread outwards and down the T-tubules
- The DHP voltage sensors are activated and pulls on the Ca++ release channel door
- The Ca++ release channels are opened and Ca++ floods into the skeletal muscle cells
- The muscle contracts
- The SERCA pump returns Ca++ back into the SR
What is EPP
End plate potential
What is the sarcoplasm?
Fluid inside of muscle cells
similar to cytoplasm
Why are there lots of mitochondria in the motor neuron?
Ion pumps that use ATP
Ach storage vessicles have ATP in them to help move the vessicle
A source for acetate THINK used for Ach
Why are there lots of mitochondria in the skeletal muscles?
Alot of energy needed for contractions/twitches
SERCA pump is ALWAYS working
What is Ach broken down by and what happens to it afterwards?
Acetylcholinesterase
Choline and Acetate are reuptaked back into the motor neuron
Why is Acetate not recycled as much as acetate in the motor neuron?
Because mitochondria is a source of acetate and the motor neuron has lots of mitochondria
How is Choline and Acetate recycled back into the motor neuron?
Choline ATPase pump
2nd transporter: Choline dragged with Na+
(Choline Na++ transporter)
What happens to Choline once its recyled back into the motor neuron?
Used to make Ach
Stored in the cell wall as Phosphatidylcholine until needed
What helps reset both the motor neuron and the skeletal muscle after an AP?
Ca+ ATP pump
Na+/K+ ATP pump
Leaky K+ channels
What is Myastenia Gravis?
MG
A immune system response to inflammation of the thymus gland
What happens during MG?
Body generates antibodies to nAch receptors
Antibodies attach to nAch receptors and destroys them
scar tissue left over decreases the surface area of the clefts in the skeletal muscles– fewer fast Na++ channels
Harder to generate AP
MG gets worse throughout the day
What is Tx for MG?
Remove thymus gland
plasmapharesis
-stigmine drugs (neostigmine)
What is a neostigmine?
Acetylcholinesterase inhibitor
allowing more free Ach at the NMJ will increase the probability of interaction and binding time to the nAch receptor to generate an AP
What is LEMS?
Lambert-Eaton Myastenic Syndrome
-Similar to MG
-Paraneoplastic syndrome (developed with cancer) usually with lungs
-Motor neuron dependent disease
-Body generates antibodies to P-type Ca++ channels
-P-type channels destroyed preventing Ca++ from going into motor neuron
-Ach vessicles never come to NMJ to be released
What is the treatment for LEMS?
NOT NEOSTIGMINE!!!!!!
-plasmapheresis
-remove tumor
-TEA drugs (tetra-ethyl ammonium)
What are TEA drugs (tetra-ethyl ammonium)?
They are K+ channel blockers
How does Tetra-ethyl ammoniun drugs help in LEMS?
Blocking the K+ channels will increase the time the motor neuron will be depolarized
by increasing this time, the AP has a higher probability or interacting with P-type channels that are still functional giving them more time to allow more Ca++ into the cell.
Why are TEA drugs a last resort?
They are very dangerous:
-unspecific: blocking K+ channels in the heart???? no thank you
What are 2 types of dysfuntional neuromuscular diseases?
MG and LEMS
How does curare work?
Non depolarizing paralytic
nAch antagonist/blocker: Binds to 1 of the alpha subunits on nAch receptor rindering it useless
Result is relaxed skeletal muscles
What is Succinylcholine?
Depolarizing muscle relaxant
2 acetylcholines attached to each other
T/F: Since Succinylcholine is 2 Ach, it is broken down by acetylcholinesterase.
F
acetylcholinesterase likes to break down ester bonds but with 2 Ach its harder to get to the ester bond
What happens when you give Succinylcholine?
- Drug given IV
- Drug travels to NMJ where it attaches to binding site on nAch receptors
- Depolarization of skeletal muscle for a prolonged period of time because the nAch are constantly OPEN
- Initial depolarization of the skeletal muscles will cause a twist contraction (immediate AP; not every muscle twitches at once)
- Prolonged opening of the nAch receptors allows Na+ to keep flooding in and prevents resetting of fast Na+ preventing anothering AP
**Fast Na+ channels should be stuck in inactivated form (M-gate open; H-gate closed)
How long is the nAch open with an AP?
1 ms
How long does Succinylcholine keep the nAch receptor open and depolarize the skeletal muscle cell?
up to 10 minutes
What is first pass refer to when giving Succinylcholine?
Twitch contractions throughout the body as a result of the initial opening of the nAch receptors on different muscle groups which generated an AP
Where are nAch receptors located?
On the skeletal muscle on the post synapse at the NMJ; inside clefts
T/F: nAch receptors are located everywhere on the skeletal muscle
F
What happens to K+ when giving Succinylcholine?
Since Na+ is flooding into the cell making it more positive this is wanting to push K out of the cell.
This INCREASE K+ in the ECF
influx in serum K+ can cause cardiac arrythmias
How much can depolarizing skeletal muscle blockers raise serum K+?
0.5mEq/L in a healthy person without hyperkalemia pr bradycardia
What happens when you have a stroke or prolonged inactivity of skeletal muscle cells? And you give succs?
nAch Receptors may develop OUTSIDE the NMJ
Results in greater K+ loss when Succs is given
Increases Serum K+ faster through leak K+ channels
