Exam 3 - Lecture 7 Flashcards
A-band on microscope
Entire dark area
Length-tension relationship
Essentially is looking at how well a muscle is being stretched out. Tension developed in % is the y axis, length of sarcomere is X axis. If its under or overstretched, you get less force.
The length-tension relationship is measuring the
active tension
Passive tension
The stretch/pulling force put on the muscle, no contraction involved (not being produced by muscle by action potential)
Active tension
Muscle contraction, when an action potential hits the muscle and causes it to shorten.
Total tension
Active + passive tension.
If you subtract passive tension from total tension, you get
active tension
If we use a really heavy weight, it’ll __________ the muscle and it ___________
Overstretch; wont contract
Load/contraction velocity diagram
Increased load = Decreased muscle contraction speed.
The heavier the load, the slower the muscle will contract.
Quantal summation
Recruiting more and more motor units (number of) to generate more muscle contraction. Regulated in a step-like fashion by recruiting additional motor units one by one, and each additional unit produces a quantum of force, and the overall force is the sum of these quanta.
Where is load/contraction velocity diagram most important?
Cardiac muscle, as excessive load (fluid) could make the heart take longer to eject the blood which interrupts the next cycle
Voltage/recruitment
Recruiting larger and larger motor units, takes more voltage to recruit the larger muscles, voltage refers to strength of electrical stimulus.
Temporal (time) summation
This involves the timing or frequency of stimulation. When stimuli are applied to a muscle in rapid succession, the muscle has less and less time to relax between stimuli. This results in increased force with each stimulus, as the twitched begin to add up (summate) over time. More frequent, the stronger the contraction.
hertz is
number of stimuli per second, so 1hz is 1 stimuli per second.
After about 10-12 hertz, the twitches become
additive and not allowing the muscle to fully relax before contracting again.
The muscle is continuing to contract, adding on top of each other.
Ca++ is coming out of the sarcoplasmic reticulum faster than it can be put back in.
Tetanization
At roughly 40hz, we have so much calcium inside the cell, we are now longer seeing twitches in the muscle because the calcium receptors in the muscle are saturated.
Generates 3x as much force as it recruits more motor units.
Tetany
State of sustained muscle contraction that occurs when stimuli are delivered so rapidly that the muscle does not have time to relax between stimuli, leading to maximal and continuous contraction. May be incomplete (slight relaxation in between stimuli) or complete (smooth, sustained contraction)
If we dont use our muscles for a long period of time, ________ can occur.
Atrophy
Atrophy leads to what specifically?
Losing the myofibrils within the cells, leading to atrophy. If its an extended period of time, the entire muscle cell can start to disappear.
Skeletal muscle cells are difficult to
replace
If you have a spinal cord injury, you’ll need to pay someone to come and _______, if you have hopes that you will someday regain the ability to move these muscles.
Stimulate your muscles with action potentials to keep them alive and prevent complete atrophy
Hypertrophy
Adding myofibrils to skeletal muscle cells.
A large part of tissue mass will be blood vessel network in skeletal muscle, increases vascular bed size.
Hyperplasia
Happens at a very low rate, creates new skeletal muscle cells.He
Heart muscle is capable of replacing _________ but happens at__________
Dead cells; a very slow rate.
If you have minimal cardiac injury, heart can ________ recover. But not ___________.
replicate cells slowly and; for a large injury.
The downside of anything that increases cell division/regrowth is that it
Increases chance of cancer.
Smooth vs skeletal muscle (5 things)
Stronger (per gram basis)
More efficient
A little slower
Slower cross-bridge cycling
Latch mechanism
Skeletal is _____ of body weight and smooth muscle is ________ of our body weight.
40%;10%
Parts of body that has smooth muscle
intestines, blood vessels, lungs (and all over the place)
Smooth muscle has much more _____ than skeletal muscle
Variety/specialized
why is smooth muscle more efficient?
The cross-bridge cycling occurs at a much slower pace, and it takes the myosin heads longer to release from the actin filaments, conserving some of the tension.
Latch mechanism
Slower cross-bridge cycling on steroids, to the point where myosin heads are difficult to be removed, maintaining force that was previously generated, and the myosin head just hangs onto actin molecules. Smooth muscle maintains force of contraction for a long time while using very little energy. In the skeletal muscle, its constantly using ATP to maintain the same contraction.
Structure of vascular smooth muscle from out to in
Adventitia, Medial muscle fibers, endothelium
Smooth muscles are connected to neighbors via
Gap junctions
Actin to myosin ratio in skeletal muscle
2:1
Actin to myosin ratio in smooth muscle
10-20:1
Myosin to actin ratio in skeletal muscle
1:2
Myosin to actin ratio in smooth muscle
1:10-20
Much more _______ than ________ in smooth muscle
actin; myosin
Equivalent to Z-discs in smooth muscle
Dense bodies. Spherical shaped bodies that actin is anchored to.
What are dense bodies connected to?
Actin and are also structurally linked to neighboring smooth muscle cells, and is used as an anchor to use force.
Amount of calcium in internal storage for smooth muscle
Much less than in skeletal muscle, SR is less developed than cardiac and skeletal muscle.
Smooth muscle is dependent on ______ calcium
outside
A less well-developed SR will have less _____
calcium
How does calcium get into smooth muscle cells?
Leak, voltage gated, or ligand gated
Why can you have low blood pressure in relation to calcium?
Hypocalcemia can cause low blood pressure cause smooth muscle doesn’t have enough calcium to constrict the blood vessels, and the heart doesn’t eject as much blood for same reason. But it is more related to lack of vasoconstriction.
Most smooth muscle is set up in what fashion? And what are they called?
unitary fashion, functioning as a unit so what happens in one muscle cell, is what also happens to its neighbors via gap junctions, and these are called visceral smooth muscle cells
Intestinal smooth muscle functions as
visceral smooth muscle
Multi-unit smooth muscle and what it allow for?
No pathways for ions to move between neighboring cells, allowing for graded/precise/delicate control.
Mult-unit smooth muscle is entirely dependent on ____ to tell it what to do?
Neurotransmitter in the area
Ciliary and iris muscles in the eye are gonna use what type of smooth muscle?
Multi-unit, because it needs fine-tuned accurate control.
Vast majority of the body uses
visceral smooth muscle
Vascular smooth muscle uses what type of smooth muscle?
Visceral smooth muscle
Esophagus is the oddball muscle why?
hybrid muscle where it uses smooth muscle and skeletal muscle.
Adventitia
structural support, outermost layer of vascular smooth muscle
Endothelial cells
Innermost layer of entire circulatory system in every blood vessel
Almost every blood vessel will have
smooth muscle
The only blood vessel that doesnt have smooth muscle will be and what is exclusively?
capillaries, which are made exclusively of endothelium
Chambers of our hearts also have
endothelium
Alternate names for layers of arterial blood vessels
Tunica intima: endothelium
Tunica media: medial muscle fibers
Tunica adventitia/externa: adventitia
The different layers of the arterial blood vessels can _______ with another. How do they do it?
communicate through neurotransmitters or gases such as nitric oxide
just the endothelium and medial muscle fibers communicate, not the adventitia
On skeletal muscle, there is a gap in middle where there arent any
myosin heads and it differentiates between left and right side of myosin molecule.
Structure of myosin heads when they are relaxed vs when they are contracted in skeletal muscle?
At relaxation they appear to be angled inwards towards center line, and at contraction they appear to be facing away from the center line
In smooth muscle, is there a middle m-line in the myosin heads?
no
Structure of myosin heads in smooth muscle looks like?
slanted
What can shorten more, smooth muscle or skeletal muscle?
Smooth muscle by a lot.
If we have a 2micrometer smooth muscle, it can shorten its length how much?
in half or more
If theres a large skeletal muscle, how much does it shorten?
Only a couple cm’s
Neurotransmitter for skeletal muscle is always
acetylcholine
Does smooth muscle use acetylcholine NT?
yes, plus others and plus they do different things depending on where they are.
e.g. mACh-r may relax or excite based on type of cell they are stimulating
Typically, acetylcholine receptors in vascular beds will mediate
relaxation
Typically, acetylcholine receptors in small intestine will mediate
contraction
Pacemaker cells ion permeability in relation to resting membrane potential
Significantly higher resting membrane permeability to Na+ (#1) or Ca++ (#2)
How do active sites differ in smooth muscle vs skeletal?
Active sites in smooth muscle are always exposed.
What does the calcium bind to in smooth muscle to form a complex?
Calmodulin to form a Ca++-Calmodulin complex
What does the Ca++-Calmodulin complex activate?
Myosin light chain kinase (MCLK)
What does MCLK do after its activated by Ca++-Calmodulin complex?
MCLK will then phosphorylate the myosin light chain (MLC) leading to contraction of smooth muscle.
What happens after Ca++ concentration decreases after contraction?
Ca++ decreases due to pumping of Ca++ out of the cell, and then the process is reversed and myosin phosphatase removes the phosphate from the MLC, leading to relaxation.
What does myosin phosphatase do?
Removes phosphate from MLC
The actin we have in smooth muscle, does not have the active sites _______
hidden
Is tropomyosin present in smooth muscle?
Yes, just not doing anything like in skeletal muscle.
In smooth muscle, the myosin head is not always
turned on
When the regulatory light chain is phosphorylated in smooth muscle, then it is
activated
Myosin light chain kinase (what does it phosphorylation SPECIFICALLY?)
Sticks phosphates to regulatory light chain of myosin molecule in smooth muscle, leading to contraction.
What determines MLCK?
How much calcium we have floating around in the cell
In smooth muscle, calmodulin binds to a bunch of calcium and it
wraps itself around the MLCK and activates it
Most calcium for smooth muscle comes from
outside the cell, some comes from SR but typically not as well developed as skeletal muscle
real important voltage gated ion channel in smooth muscle? speed of them and how long do they stay open? Is it the most common way for that ion to enter the cell?
L-type calcium channel. Typically slow and stay open for a longer period of time.
Most common way of calcium coming into smooth muscle cell.
How does the smooth muscle relax/stop contracting?
Myosin head would have to go back down, by removing phosphates from myosin heads.
or prevent myosin from binding in first place (reducing calcium intracellularly)
Myosin phosphatase
pulls phosphate off of myosin head and inactivates myosin molecules.
How to remove calcium from smooth muscle cell?
SERCA pump to put it back in SR
Calcium removal pumps = PMCA (Plasma membrane calcium ATPase pump) and it works very similar to SERCA.
Sodium-calcium exchanger (3 Na+ in, 1 Ca++ out)
what cleans up sodium that comes into smooth muscle cell as a result of sodium-calcium exchanger?
Na+/K+ pump
What’s the main way to remove calcium from smooth muscle cell?
Sodium-calcium exchanger (3 Na+ in, 1 Ca++ out)
How can calcium get into VSMC?
Leak or voltage-gated
Steps of what happens after calcium enters VSMC? what happens eventually?
Leak in or through slow voltage gated channels -> bind with calmodulin -> turns on MLCK -> phosphorylates myosin light chain (equals Myosin-LC-PO4</sub) = Contraction
Phosphates fall off and more relaxation we get/less contraction. (Myosin-LC)
or Myosin phosphatase removes phosphate from myosin light chain.
How do we prevent myosin-LC-PO4?
reduce activity of MLCK by pumping out calcium or use nitrates which will reduce activity of MLCK.
What do nitrates do in the VSMC?
Increase production of cGMP
What does cGMP do in VSMC?
Change activity level of kinases
Kinase that responds to cGMP in VSMC?
Protein kinase G (PKG)
What is the result of more cGMP in VSMC?
more PKG
results in relaxation/less contraction.
What does PKG do in the vascular smooth muscle cell?
Sticks phosphates on MLCK-> reduces the activity of MLCK -> reduces phosphates being stuck to myosin heads = relaxation/less contraction of vascular smooth muscle.
Where are nitrates coming from? How?
Endothelial cells.
L-arginine turns into Nitric oxide (NO) via activity of endothelial nitric oxide synthase (eNOS)
Another target for PKG in VSMC
Calcium entry pathways, it phosphorylates the calcium entry channels and closes them down.
What increases activity of eNOS?
Neurotransmitters/signaling compounds (Acetylcholine or bradykinin), which interact with endothelial cells which will talk to smooth muscle cells.
Acetylcholine/bradykinin bind to mACh-r in endothelial cells which results in (the answer is the entire cycle)
release of calcium from calcium stores of endothelial cells (in ER) -> calcium binds with calmodulin and changes its shape -> results in eNOS -> acts on L-arginine to form NO, which is a gas and it diffuses outside of endothelial cell and interacts with targets in smooth muscle cell -> target is soluble guanylyl cyclase -> takes GTP and turns it into cGMP -> upregulates PKG -> phosphorylates targets to inhibit contraction such as Ca++ channels and MLCK.
cGMP is unstable and _________. How can we speed this up?
can fall apart on its own.
Enzyme called phosphodiesterase will shut down cGMP really quickly
If we inhibit phosphodiesterase in VSMC, what’s the result? what’s the drug used as an example?
prolonging life of cGMP, you’re inhibiting an inhibitor… so it will result in increased relaxation.
e.g. sildenafil
what is sildenafil and how does it work
Phosphodiesterase inhibitor (Decreases amount of Phosphodiesterase, which breaks down cGMP, decreases PKG, and increases contraction)
increases cGMP -> increases PKG -> vascular relaxation.
what happened during sildenafil drug study?
It was originally for pulmonary HTN.. didn’t work, so after a few months the researchers asked the participants to bring the drugs back, and they didn’t….
How to elicit a reaction in smooth muscle via alpha1 receptors?
(alpha agonists)
agonist binds to a1 receptor -> increased phospholipase C -> snips big chemical into IP3 (inositoltriphosphate) -> IP3 releases calcium from SR) -> binds to calmodulin -> activates cross-bridge cycling of myosin head = contraction
what else gets released by phospholipase C?
other than IP3…
DAG is a byproduct that gets released by phospholipase C that increases activity of protein kinase C that further contracts smooth muscle.
Serotonins effect on smooth muscle
Constricts smooth vessels and activates same phospholipase C pathway as a1 receptors
Only neurotransmitter that can constrict brain blood vessels
Serotonin (via phospholipase C pathway)
SSRI’s can be useful for things like (think vascular, not depression)
headaches bc it increases tone of blood vessels in brain and reduce pressure.
Smooth muscle can generate __________, but it doesnt need to for the muscle to __________
action potential; contract.
What is enough to cause a contraction in smooth muscle independently of an action potential?
Leaky calcium
What ion is not necessary for smooth muscle contraction?
Calcium is not necessary, but it is usually what starts everything needed for a contraction.
Uterus action potential lasts how long? What kind of channel is it (speed and name)?
Quarter of a second
Slow, L-type calcium channel
Pacemaker activity action potential and in what organ?
Rhythmic action potential, going up and down, small intestine.
Some smooth muscles have the ability to generate _________ potentials which help with moving things along a corridor (such as the ____________). It generates an AP every _______ seconds.
pacemaker; smooth muscle in small intestine; 10-20 seconds
What’s causing the muscle cramps to happen every 20-30 seconds?
Pacemaker type action potential
Cardiac muscle cell is very similar to _________ as far as the arrangement of the __________
skeletal muscle; sarcomeres
Vast majority of calcium that drives heart contraction comes from
internal stores of heart cell, it has a well-developed SR with lots of calcium stored in there.
what triggers release of calcium from SR in heart muscle? Whats it called?
extracellular calcium influx
“Calcium induced calcium release” aka CICR
In heart cells, How much calcium is involved in coming in from outside and releasing internal stores?
1:4 ratio. 80% of calcium being used in heart contraction comes from SR, 20% from outside.
How does calcium come in from outside the cardiac cell? and the order of the channels as they occur?
first to be involved is “Fast” T-type calcium channels (faster to open and faster to close)
then slow L-type calcium channels “a little bit later”
What triggers the calcium to enter the cell from the outside?
Action potential that conducts through heart cell, dependent upon sodium coming in through fast sodium channels.
In a cardiac action potential, the deep upstroke is
sodium induced action potential that opens fast sodium channels
In the heart, we have very large
T-tubules
A major source of the calcium that comes into heart cell from outside, is parked right in the
large t-tubules
80% of the calcium in the cardiac cell during recovery is placed back into the SR by
SERCA pump
Primary pathway of calcium exiting via cell wall in heart
sodium-calcium exchanger 3:1 ratio
does the heavy lifting
Secondary pathway of calcium exiting via cell wall in heart and when is it used?
Calcium ATPase in cell wall (Plasma membrane calcium ATPase, aka PMCA)
usually used towards the end of the calcium removal process cause its a strong pump and can work on very low levels of calcium inside the cell.
Calsequestrin: where is it found and what does it do?
found in SR of ALL muscle cells
Sequestering protein (takes things out of circulation): sees calcium in SR and binds to it to store it. A way to store more calcium in a small container. It takes the calcium out of the solution and it makes it easier on serca pump to fit more calcium into SR. Very efficient and helps concentrate calcium.
Differences between SR in cardiac muscle vs smooth/skeletal muscle
Neither smooth nor skeletal have modulator of SERCA pump, called phospholamban.
It inhibits SERCA pump, which allows calcium to hangout in sarcoplasm for longer.
Results in longer contraction.
What would inhibition of phospholamban do and what type of drugs?
inhibition would lead to shorter contractions, and resets the cell faster, faster heart rate.
usually drugs that’s purpose is to increase your heart rate
neurotransmitters or signaling compounds that heart cells respond to
things that bind to acetylcholine or adrenergic receptors, typically to antagonize one another.
The more catecholamine in the heart, faster the heart
The more cholinergic, slower the heart rate
Big antagonism relationship system in heart muscle cells, not including what area?
cholinergic vs beta, OUTSIDE (not including) THE NODAL AREAS
Heart muscle cells have what receptors
catecholamine/beta and cholinergic
Beta receptor stimulation causes?
Stimulation of adenylyl cyclase -> turns ATP into cAMP -> cAMP increases PKA activity -> increased inotropic/chronotropic response
Beta agonism results in higher what?
higher PKA activity
mACH-r binding results in what?
acetylcholine binds, which tells adenylyl cyclase to slow down, resulting in less PKA activity
Most cardiac muscle cells are programmed to be able to talk to both
beta and cholinergic agonists
mACH-r slowing down heart rate is more specialized to what?
nodal conduction tissue since that’s where heart pacemaker is
The antagonistic relationship of cholinergic and beta is not in relation to this specialized activity.
