Skeletal muscle Flashcards
Location and function:
Na/K/ATPase
skeletal fiber/muscle cell membrane
Location and Function
Ca ATPase
Sarcoplasmic reticulum
Sequesters Ca
Location and Function
Ryanodine receptor
Terminal Cisternae part of the SR
Large Ca release channels
Location and Function
Dihydropyridine receptor
Slow v-gated Ca channels
Essential for excitation contraction coupling
Located in transverse tubules (invagination into the muscle fiber)
Location and function
actin
Isotropic/light band- made of thin actin filaments
Z disc on ends, middle is H, A next to H, I next to A with Z disc in the middle
Location and function
Myosin
A band - made of thick myosin filaments
Z on ends, H in middle, A next out from H
Location and function
Troponin
Found on the actin thin filaments
Regulatory proteins
Ca sensor for the contractile proteins
What benefit doe muscle cells reap from a high RMP to Cl-?
RMP btwn -80 and -90 mV
ECF in t tubules and over many AP, there will be a build up of K - which will keep cell excitable/depolarized. High Cl permeability. Stabilizer. Can enter the cell. Return the cell to more negative RMP. Electrically stabilize skeletal muscle.
How is an AP on the surface of a muscle cell able to interact with muscle components on the interior of a cell that may be 100 uM in diameter?
Muscle cells are as long as the muscle - and up to 100 uM in diameter
Types of energy sources that power muscle function
ATP is required for skeletal muscle. ATP is produced by:
1. Substrate phosphorylation is the immediate production of ATP through creatine phosphokinase (CPK). CPK removes the phosphate from creatine poshphate and puts it on ADP to make ATP and creatine (phosphocreatine + ADP = creatine + ATP). The cell has about 20 mM phosphocreatine to drive this process.
- Glycogen is stored in muscle and can be broken down into glucose 6 phosphate which can then be shuttled into glycolysis fort he fast anaerobic production of ATP in the cytoplasm. In absence of O2, pyruvic acid can be converted to lactic acid to maintain NAD+ for continued glycolysis. Glycolysis nets 2 ATP for every molecule of glucose. (int twitch, fast glycolytic - fatigue quickly. Bigger, white.)
- Oxidative metabolism is the burning of fatty acids and pyruvate w/in the mitochondria via the Krebs cycle and oxidative phosphorylation. The high energy compounds from the Krebs cycle donate their electrons to the electron transport chain. CO2, water and 36 ATP are produced as a result. (slow twitch, small amt of tension but can go on forever like posture - lots of mitochondria, lots of oxygen)
Parts of the NMJ
The synapse btwn an alpha motor neuron and a skeletal muscle fiber.
Steps of synaptic transmission
- AP is propagated along alpha moto neuron
- V-gated Ca channels in the axon terminus are opened
- Ca influx at axon terminal stimulates exocytosis of ACH vesicles and release of ACH into the synaptic cleft.
- ACH diffuses across synaptic cleft and binds to cholinergic nicotinic receptors on post synaptic membrane (motor end plate)
- ACH receptor is a large cationic channel that produces an excitatory postsynaptic even called the endplate potential (Na, Ca in - K out)
- Opening of the ACH receptor causes a lg depolarization at the MEP (lg channel that allows + ions to pass through)
- This causes a net inward current that depolarizes the cells to threshold - more Na+ in than K+ leaves.
- Depolarization of the MEP brings the surrounding membrane containing fast v-gated Na+ channels to threshold so the AP can propagate along the sarcolemma
- ACH is removed bc it is hydrolyzed by acetylcholinesterase. The presynaptic axon takes up choline for resynthesis of aCH and acetate is taken up by all cells for metabolism.
- Reach threshold
- Depolarization opens up v-gated Na channels and then we can propagate AP along sarcolemma
How doe the NMJ differ from a CNS synapse?
NMJ - one neuron can synapse on several different fibers (motor unit) but each fiber only has one synapse.
Motor end plate potential is a lot larger. Usually CNS postsynaptic potentials are very small - therefore, the presynaptic input of many neurons is require in order to stimulate the post synaptic cell. However, at the NMJ, 1 motor neuron produces a PSP of 60 mV and the motor EPP is lg enough to be suprathreshold. As a result, an AP in a n alpha motor neuron causes an AP in the muscle. Even though larger, has the same properties and ss as other PSP.
Color of:
Slow
Intermediate
Fast
Red
Red
White
Myoglobin of:
Slow
Intermediate
Fast
High
Low
Low
Capillaries of:
Slow
Intermediate
Fast
Dense
Med
Scarce
Mitochondria of:
Slow
Intermediate
Fast
Many
Med
Few
What are the parts of a twitch?
Single unit of muscle contraction. One AP in a motor neuron leads to a twitch in all the fibers w/in the unit
How does a twitch follow all or none?
A single twitch stimulation is a stimulus strong enough to recruit all muscle fibers in a neuronal pool (all of the motor units in the muscle) but short enough in duration and slow enough in frequency that twitches do not start to fuse.
How would a hormone that acts by ________ impact smooth muscle tension?
Increase NO
Activates cGMP, causing vasodilation
How would a hormone that acts by ________ impact smooth muscle tension?
Increase cAMP
Promote relaxation through enhanced Ca reuptake and enhancement of the phosphatase activity
How would a hormone that acts by ________ impact smooth muscle tension?
Increase cGMP
Promote relaxation through enhanced Ca reuptake and enhancement of the phosphatase activity
How would a hormone that acts by ________ impact smooth muscle tension?
open CA channels
Cause smooth muscle contraction
How would a hormone that acts by ________ impact smooth muscle tension?
open K channels
Hyperpolarize the cell membrane and make contraction less likely
How would a hormone that acts by ________ impact smooth muscle tension?
Increase IP3
Incrase intracellular calcium, increasing contractility
Substrates of:
Slow
Intermediate
Fast
lipids, COH, AA
mostly COH
COH
Smooth muscle
NE
contraction via alpha 1 receptors
Smooth muscle
Epi
relaxation via beta receptors
Smooth muscle
ACH
activation of GI muscle
Smooth muscle
angiotensin II
vasoconstrictor
Smooth muscle
ADH
effects like vasopressin
Smooth muscle
oxytocin
uterine contraction through G protein coupled calcium channels
Smooth muscle
Serotonin
Vasoconstrictor
Smooth muscle
Histamine
Dilation and increased permeability of systemic vessels
How is ACH reuptake affected by drugs?
Non-depolarizing blockers, like roc, bind to the alpha subunits and prevent the channel from opening.
Succ binds to the channel, opens it and keeps it open, therefore Succ is a depolarizing NMB.
To reverse a blocked channel, inhibitors of Acetylcholinesterase are applied. OR Sugammadex, which has a lipophilic core, attracts roc and reverses the NMJ block w/o affecting the acetylcholinesterase in muscarine synapses. This permits reversal w fewer side effects.
How is ACH reuptake affected by drugs?
Non-depolarizing blockers, like roc, bind to the alpha subunits and prevent the channel from opening.
Succ binds to the channel, opens it and keeps it open, therefore Succ is a depolarizing NMB.
To reverse a blocked channel, inhibitors of Acetylcholinesterase are applied. OR Sugammadex, which has a lipophilic core, attracts roc and reverses the NMJ block w/o affecting the acetylcholinesterase in muscarine synapses. This permits reversal w fewer side effects.
Myasthenia Gravis
Autoimmune disorder of NMJ
Antibodies to the ACH reuptake fare formed. Block the receptor which decreases the binding sites from ACH in the MEP.
Result is a reduction in the MEP potential and therefore muscle weakness in the eyelids, arms and chest.
Treatment is drugs that inhibit acetylcholinesterase (neostigmine) and steroids or thymectomy
What are the cellular events that lead to Ca2+ release from the SR?
When an AP travels in t-tubule, it meets a DHPR, which is a v-gated Ca channel, causing Ca to be released in large amounts from lateral sacks of SR.
What molecular events occur during muscle contraction?
EXCITATION/COUPLING
Sacrolemma - an AP is going to travel along the sarcolemma into T tubule, will travel along until it meets a DHPR.
The DHPR is a ca channel - but more importantly, it is v-gated. B/c of this, it has a dipole (neg and pos charge that can be flipped by a different electrical env’t). So when the dipole is flipped in this DHP, causes the ryanodine receptor (ca release channel) in the enlarged sacks of SR to open.
Large amounts of Ca is released from SR and diffuses into the cytoplasm around the contractile apparatus. It finds and binds to troponin.
Troponin changes shape which pulls on tropomysin, which reveals binding sites on actin. The myosin heads can bind to actin binding site. Myosin does a power stroke. This allows actin to slide along the myosin.
When actin and myosin are sliding, the sarcomere shortens. This causes myofibrils to shorten. This causes the cell fiber to shorten. When all the cell fibers shorten, the muscle shortens.
How do muscle cells relax?
In the longitudinal portion of SR, there is a Ca/ATP-ase
Ca+ is pumped back into SR so there is a gradient for Ca to leave. When Ca is pumped back into the SR and Ca release stops, then Ca is removed from cytoplasm.
This permits the contractile apparatus to relax.
Isometric contractions
Same length
Muscle fiber is stimulated but we don’t allow it to shorten. Generate tension
Short latent period, contraction, relaxation phase
Isotonic contractions.
Same load/same tone
shortening contractions
A fiber is stimulated, shortened and pull a load
Longer latent period b/c initially you have to contract and generate enough tension to lift the load. In the latent period is an isometric contraction that we can’t measure. Then becomes isotonic.
We can do work with this type of contraction
Describe the series elastic component of a muscle?
x
Compare and contrast the relationship between length and tension for a muscle fiber and a whole muscle.
2.2 uM is best length of sarcomere to have a good contraction. Here, we see a good amt of overlap btwn myosin and actin so when Ca comes along, we can grab cross bridges and can shorten.
If muscle starts out too short, the muscle is all disorganized - all smushed up. Myosin heads all over the place - grabbing the wrong actin. You don’t get the best tension. DISORDERED that interferes with ability to contract.
If muscle too stretched, hardly any overlap btwn myosin and actin so really hard to get contraction going and tension drops.
As we stretch the muscle, the tension in the muscle goes up and we get peak tension. As we stretch muscle more and more and disrupt overlap btwn myosin and actin and lose tension. but then it goes up again - “false tension” from connective tissue. We get a high amt of tension but not from cross bridges but bc we are stretching connective tissue. This is PASSIVE tension, masking the fact that active tension is going down.
How does one load a muscle?
Light load - we can do a lot of this, very quickly
Int load - we pay not pull it as far (probably most efficient)
Heavy load - may hardly lift it - may become isometric load
What does muscle loading do to contraction velocity?
No load - can shorten fast
As we add a load, the contraction gets slower and slower until load is so heavy that we can’t lift it. There might be a load so heavy, makes muscles lengthen.
If a twitch is all or none, why is a muscle contraction graded? Include recruitment and tetany in your answer.
AP happens very quickly. Releasing Ca. A twitch takes 100 ms. If we stimulate, before the twitch has the ability to relax, and we stimulate again, we add a twitch on top of it and so on. Our whole tension gets bigger and bigger - we stimulate so much that whole fiber doesn’t have a chance to relax. Tetanus.
With a big contraction, Ca release is high and steady. It exceeds ability of SR to pump it back in. Allowing us to maintain prolonged contraction.
Eventually - fatigue. Rest a bit. We stimulate it, we give it a tetanic stimulus and fatigue happens even faster.
Another way to build a contraction is to add motor units. RECRUITMENT. We stimulate muscle, we get a motor unit. We increase the stimulus, we get another motor unit and our tension goes up. And so on.
Slow twitch - don’t fatigue. but stick around a lot. Lower threshold, and they are recruited 1st. Then the middle sized ones, then the big ones.
What is the size principle?
Motor unit recruitment is a measure of how many motor neurons are activated in a particular muscle, and therefore is a measure of how many muscle fibers of that muscle are activated. The higher the recruitment the stronger the muscle contraction will be. Motor units are generally recruited in order of smallest to largest (smallest motor neurons to largest motor neurons, and thus slow to fast twitch) as contraction increases.
What receptor systems report to the CNS on length and tension information from muscle? Where are these receptors located?
Muscle spindles are stretch receptors within the body of a muscle that primarily detect changes in the length of the muscle. They convey length information to the central nervous system via afferent nerve fibers. This information can be processed by the brain to determine the position of body parts.
The responses of muscle spindles to changes in length also play an important role in regulating the contraction of muscles, by activating motor neurons via the stretch reflex to resist muscle stretch.
The muscle spindle has both sensory and motor components.
Sensory information conveyed by primary type Ia sensory fibers and secondary type II sensory fibers, which spiral around muscle fibres within the spindle
Motor action by up to a dozen gamma motor neurons and to a lesser extent by one or two beta motor neurons that activate muscle fibres within the spindle.
physiologic and clinical definitions of post-tetanic potentiation.
High rate of AP so we see fusion of the twitches - smooth contraction
In the clinic, we give pt a twitch stimuls, then a tetanic, then another twitch. 2nd twitch is bigger. This is bc a we have a build up of Ca in the cell. When we stimulate it the second time, more Ca and therefore bigger twitch.
What is coactivation of muscle pairs? What is the benefit of this activation pattern?
Pt of origin - attachment that doesn’t move.
Insertion.
When bicep contracts, moves the muscle up.
Antagonist is tricep. It pulls the arm so it extends.
Your brain activates both in co-activation. This stabilizes the joint. Controls the load.
ALSO - The muscle attaches to these bones acts as lever system. IF we want to move a heavy load, move fulcrum close to the load to be powerful, but we lose how high we can move the load. Human skeletal muscle system and bones - work together to balance power with range of motion.
Compare and contrast the microanatomy and physiology of smooth and skeletal muscle.
smooth muscle can contract in all different directions, which is good for squeezing. Actin is crisscrossing all over the place
Much smaller
Skeletal muscle:
- Incrase Ca
- Ca binds to troponin on thin filaments
- Conformational change in troponin moves tropomyosin out of the blocking position
- Myosin cross-bridges bind to actin
- Cross-bridges cycle produces tension and shortening.
Smooth muscle
1. Increase in Ca
2. Ca binds to calmodulin in cytosol
3. Ca-calmodulin complex binds to myosin light-chain kinase
4. Myosin light-chain kinase uses ATP to phosphorylate myosin cross-bridges
5. Phosphorylated cross-bridges bind to actin filaments
6. Cross-bridge cycle produces tension and shortening
More kinase = more contractions
More phosphatase = more relaxation
What is the BER?
Basal electrical rhythm
- slow wave, below threshold.
- then apply stimulus
- above threshold
- now we have Ca AP and muscle contracts
Gut
Malignant hyperthermia
genetic
halogenated anesthetics will cause an inappropriate release of CA, intense contractures, heat production and lactic acidosis
Diagnosed by muscle biopsy
NaDantrolene treatment, which blocks DHPR and blocks Ca release.
if not recognized will result in death
Multi - unit smooth muscle
innervated
Need a neuron to tell them what to do
Not spontaneous contracting
goosebumps, lens, iris
Single unit/visceral smooth muscle
connected by gap junctions so when one contracts, they all contract. ACTIVATED: Hormones, PM, NTz from varicosities, stretch sensitive
Ex: gut, pregnant uterus
vascular is in-between single and multi - it’s own category
