Exam 2 - Lecture 7 Flashcards
Largest container in the body
Skeletal muscle.
Skeletal muscles keep up _______ and you take them offline with _________? Why?
body temperature; Anesthetic, reduce skeletal muscle activity.
Every skeletal muscle has some _____
Motor neuron.
Vast majority of skeletal muscles have ______ neuron(s).
- SOME have more than 1 motor neuron innervation.
Which muscle group has more than 1 motor neuron per skeletal muscle?
Ocular muscles in eye sockets.
Motor neuron cell body is inside _______ of the spinal cord.
Anterior horn in the grey matter.
Motor neuron cells are excited by _____ pathways in the spinal cord, and _________.
Descending pathways from brain, and reflex arcs such as pain giving a strong signal, reflex arcs get involved in same level of cord.
Skeletal muscle fibers is another term for
groups of cells in skeletal muscle.
Some motor neurons are very large and ________
Branch multiple times to control multiple skeletal muscle cells.
Within skeletal muscle cells, there are contractile elements called
Actin/myosin
How are actin/myosin arranged
in tube like structures
Within skeletal muscle cells, they have a __________ that is similar to endoplasmic reticulum.
Sarcoplasmic reticulum (SR)
What is stored in sarcoplasmic reticulum?
Calcium
Is skeletal muscle reliant on calcium from outside the cell?
No, they have their own internal storage.
How long can some of our muscle cells be?
Over a foot long, and can be wide and thick.
Transverse tubules
Helps AP travel lengthwise across skeletal muscle, and also deep into the tissue.
In picture, they run across the width of the muscle cell.
How do AP’s run across skeletal muscle cell? (initial stimulus location, where do they travel, etc.)
Start in a NMJ in the middle and run outwards across the length of the cell
What happens to the muscle during contraction?
it shortens
Histology of skeletal muscle
-Each little branch of motor neurons has NMJ that look like little black balls.
-Each fiber has a NMJ associated with it.
-under a light microscope
-Skeletal muscle cells are extraordinarily long and much longer than in picture
3D scanning image: point out motor neuron and NMJ.
Cross-hatched zebra pattern is from
the alignment of actin and myosin
Mitochondria is copious but especially near _____ in the skeletal muscle cell
NMJ
Infoldings on skeletal muscle near NMJ
Subneural clefts
Further infoldings on subneural clefts
Secondary clefts
nACHr are typically near _______
The top surface of the subneural cleft at the top.
Whats at the bottom of the subneural clefts?
Voltage-activated Na+ channels (fast sodium channels)
Acetylcholinesterase and its purpose
Breaks down acetylcholine into acetyl (aka acetate) and choline.
To give it a finite time period of depolarization, helps shut it down and reset.
What produces/releases acetylcholinesterase? Where does it park it?
The skeletal muscle. At the NMJ junction.
What does acetylcholinesterase use to break down ach?
Hydrolysis.
Acetyl is a ____ group.
Small starch group
What happens to the choline?
Recycled by the motor neuron, will reuptake into motor neuron.
What reassembles the choline into ach?
Enzymes in the motor neuron
Motor neuron is wrapped in _______ which is maintained by ________.
Myelin; Schwann cells
Where do Schwann cells hang out?
Terminal end of motor neurons
How many ach receptors we have at a typical NMJ?
5 million
How many ach receptors are activated in a typical synaptic response?
500,000 or 10%.
How many ach molecules need to be released from one motor neuron?
A bare minimum of 1 million, but usually 2 million because some of it doesn’t make it to target, it may get chopped up by acetylcholinesterase before it makes it to the receptor.
How much K+ leaves through the nACHr channels?
Very minimal.
How does potassium exit the muscle cell if it wants to?
Potassium leak channels
Curare
Found in rainforest and used for hunting prey, naturally occurring paralytic that’s an antagonist to nACHr, only needs to block one of the binding sites. Old and no one uses it clinically.
Each receptor has 5 subunits, 2 of them are
ach binding sites
Most of non-depolarizing paralytics are modeled after
Curare
Acetylcholine is released from motor neuron using _________ and it is set up by _______.
Exocytosis; calcium entering motor neuron.
Skeletal know when to respond to action potentials by
Voltage sensors called DHP receptors
DHP receptors
Dihydropyridine receptors, they are voltage sensors in cell wall/t-tubules that detect action potentials pull open Ca++ release channels (RyR) in sarcoplasmic reticulum, allowing calcium to flood out into skeletal muscle.
Where the voltage sensors located?
Cell wall and transverse tubules.
Voltage sensors are also called
DHP receptors
What do DHP receptors look like?
They appear to look like voltage sensitive calcium channels.
Instead of letting tons of outside calcium in, DHP receptors ________________________________.
physically pull on the “door” of SR to release calcium into cell.
Calcium can also come into the skeletal muscle cell through
DHP receptors/Voltage sensors, but its a very small amount and the vast majority is from SR.
When calcium is released from SR, where does it go?
Sarcoplasm
Skeletal muscles can contract __________ before they need outside calcium.
Thousands and thousands of times.
Ca++ release channel is also called
RyR (ryanodine receptor). It’s called a receptor cause its physically attached to DHP receptor/reactive to a chemical.
If you put ______ on Calcium release channel inside SR, it will __________.
Ryanodine; open up.
How does calcium get put back in SR?
SERCA: Sarcoplasmic endoplasmic reticulum calcium ATPase.
-Burns ATP to put calcium back into container against concentration gradient.
What happens to calcium shortly after its released from SR?
-Gets tucked back away into SR very shortly after it was released by SERCA pumps.
E-C coupling
Excitation contraction coupling
-The entire process of motor neuron signaling to fire an action potential and causing skeletal contraction.
Choline is pumped back into the motor neuron through 2 pumps:
-ATPase mediated pump that pumps choline back in
-Secondary active transport that moves choline/Na+ using Na+ concentration gradient.
Where is choline stored in the motor neuron?
In the cell wall, such as phosphatidylcholine
What supplies ATP for these transporters in motor neuron?
Mitochondria.
What produces acetate to be combined with choline to create ach in motor neuron?
Mitochondria.
Standard leak channels on motor neuron/skeletal cell
K+ leak channels, and fewer (than K+) Na+ leak channels.
For every action potential we have, we have to __________ K+ back ______
Pump K+ back into the cell that was leaked out during action potential.
How is action potential spread down t-tubules?
Fast Na+ channels.
If calcium gets released from SR, it causes _________
Cross-bridge cycling and muscle contraction.
VG-K+ arent really required for repolarization due to
copious leaky K+ channels, but it does speed up the repolarization process.
What is Myasthenia gravis
Body generates antibodies to nACH-r and park themselves on top of the receptor and the immune system destroys them.
What happens to the subneural clefts once the immune system destroys the receptors in MG?
They scar over. It creates less surface area and fewer fast Na+ channels, making it more difficult to make an AP in the muscle.
What causes MG?
Inflammation or genetic anomaly of thymus gland (goofy looking thymus gland).
How does MG progress throughout the day?
Gets worse as the day goes on, get more and more tired.
How to treat MG?
-Remove the thymus gland
-Plasmapheresis (but can accidentally pull more than one antibody)
-Drugs (another slide)
Drugs for MG
-stigmine. It’s an acetylcholinesterase inhibitor, which prolongs ach activity at NMJ, leading to more ACH binding.
What is LEMS or ELMS
Lambert-Eaton myasthenia syndrome
-Paraneoplastic syndrome, developed from cancer (especially lung cancer)
What antibodies develop in LEMS?
Antibodies to P-type calcium channels, which means its specific to motor function.
-Leads to less calcium entering into motor neuron and less ACH being released to start an AP.
Treatments for LEMS
-Plasmapheresis
-Remove tumor
-Drugs (another slide)
Drugs for LEMS
K+ channel blockers (Tetraethylammonium or “TEA”, and 4-5 diaminopyridine)
-Blocking K+ channels will prolong depolarization, giving Ca++ more time to enter the motor neuron, and slows down resetting process. Should result in more ACH being released.
Why are drugs for LEMS dangerous?
It’s not specific to motor neurons and it can block K+ channels in the heart. Will not go this route unless end stage cancer treatment. Horribly cardiotoxic.
Amiodarone is safe because?
It’s not a good K+ channel blocker
Non-depolarizing muscle relaxant (NDMR)
curare
Depolarizing paralytic
Succinylcholine
Succinylcholine is just two
Cholines attached to eachother
Does succinylcholine bind to nACH-r?
Yes, at both sites.
What does succinylcholine cause?
Sustained depolarization of the skeletal muscle via constantly open nACH-r.
Sux can cause depolarization to last for?
10 minutes.
Is Sux an antagonist or agonist?
Receptor agonist
Can acetylcholinesterase break down sux?
Nope, it’s very specific to breaking ester bonds, and the acetylcholinesterase can’t get in and break it.
Initial reaction from sux binding to nACH-r?
Generates action potential, a quick muscle twitch on first pass.
What happens after the muscles twitch during binding of sux?
nACH-r stay open, causing constant sodium leaking in through open receptors -> prevents fast Na+ around NMJ from resetting and the inactivation gate (inner gate) slams shut.
Paralytic only effects what area?
The area immediately around the synapse, all fast na+ channels are stuck. No additional AP’s will be triggered.
Far away from the NMJ at ends of muscle, will it be able to repolarize?
Yes, things should look pretty normal.
How does the sodium leaking in constantly during sux binding affect the Na+/k+ pump?
It has a hard time keeping up with all the sodium coming in. Membrane potential is depolarized (but not to extent of peak action potential), and K+ gets pushed out of the cell.
What causes paralysis of fast Na+ channels during sux binding?
Constant sodium leaking in through nACH-r.
How does sux affect membrane potential of skeletal muscle cell?
Membrane potential is depolarized (but not to extent of peak action potential), and K+ gets pushed out of the cell, resulting in rise of serum potassium.
How much does serum potassium rise with Sux?
Goes from 4.0 to 4.5 on average, may cause heart problems. Usually not a big deal in healthy patients with optimal conditions.
What patients will have hyperk complications with sux?
Pre-existing HyperK or slow heart rhythms, or someone who has bad skeletal muscle that could hemorrhage extra K+.
What would happen if the paralytic affected the entire skeletal muscle cell?
Much more hyperK would be released into serum.
Skeletal muscle that hasnt been used in a long period of time (such as with a stroke), can cause what issues with sux?
Skeletal muscle will put nACH-r across the entire cell, instead of just isolated to NMJ. Releases tons of HyperK.
How does skeletal muscle cell lose K+?
Copious K+ leak channels.
What are muscles good for?
Keeping body warm, locomotion, communication, and expression.
