Muscle (smooth/cardiac) Flashcards
What two ways can a muscle contract
- isotonically
- isometrically
Force generated is sufficient to move load
Isotonic (same strength)
What can determine the force-velocity relationship?
Isotonic contract
Force generated is insufficient to move weight placed on muscle (afterload)
Isometric contraction (same length)
What can determine the length-tension relationship?
Isometric contraction (same length)
Example of isometric contraction
Pressing in door frame
Afterload is above maximal force and preload is changed
Length-tension relationship
What is measured in the length tension relationship?
Active force
What does the length tension relationship show
That stretching a muscle (to a point) can increase force generated
Why does stretching a muscle increase force generated?
Stretching of a muscle allows cross bridges to form more easily because of betters alignment of actin and myosin fibers
How is skeletal muscle already set in terms of preload
It is set close to the optimal preload (length)
-bc fixed at both ends mostly
What happens when you overstretch a muscle?
Lose force generation
Preload is set, afterload is changed
Isotonic and force-velocity relationship
Muscles and afterload
Muscle will develop as much force as is needed to lift specific load
What does the isotonic and force velocity relationship determine
As load increases, the speed at which you lift decreases
- more cross bridges need to form
- slower contraction gives more cross bridges more time to form
Given Jame’s diagnosis of Duchenne muscular dystrophy, what would you except if someone experimentally excited the motor neuron to his bicep
Normal AP propagation, because the dystrophy is in the muscle, not the nerve
What is smooth muscle controlled by
Endocrine and ANS
Smooth muscle
- no conscious control
- can operate effectively when greatly stretched
- fatigue resistant
- generate resting tone-stay partially contracted
What are the two types of smooth muscle units
Single unit
Multi unit
Single unit smooth muscle cells
- GI, bladder, uterus
- cells linked by gap junctions
- littler innervation
- some can generate own AP
- all contract together to form own rhythm to expel things
Multi unit smooth muscle
- Iris, vas deferens
- each cell has its own innervation
- function as distinct muscle cells (like skeletal)
Smooth muscle appearance compared to skeletal muscle
Smaller than skeletal muscle and spindle shaped, no sarcomeres
How are actin and myosin held in place in smooth muscle
With dense bodies, intermediate filaments
Does smooth muscle have troponin
No
Has calponin and caldesmon which are similar
What kind of connections do smooth muscle have
Mechanical, can have gap junctions
Do smooth muscle have T tubules
No, by they have caveolae whihc function similarly
Does smooth muscle have SERCA or SR
Yes, but they don’t have a triad configuration
E-C coupling in smooth muscle
- extracellular calcium enters cytoplasm
- this releases Ca2+ from SR, whihc binds to calmodulin
- calmodulin activates myosin-light chain kinase (MLCK), which controls cross bridge cycling
`how does calcium enter the cytoplasm of the smooth muscle
-depolarization, ligand gated channels, or 2nd messenger gated channels
What kind of calcium release is involved in smooth muscle
Calcium induced calcium release
What does myosin-light chan kinase (MLCK) do
Phosphorylates myosin light chain
Where does the calcium come from for smooth muscle
Some in the SR
Some from outside
Where does the calcium come from for skeletal muscle
ALL Ca2+ from SR
Calcium entry through the 2nd messenger gated channels
- hormones of NT activate Gq receptors, which make IP3
- directly open IP3 gate channels on SR
- IP3 dependent Ca2+ opens other Ca2+ channels
Calcium enters into smooth muscle via depolarization
- spread through gap junctions, opens VGCC on cell surface
- this calcium can open RyR channels on the SR to increase calcium more
Calcium enters into smooth muscle via ligand gated channels
- hormones and NT open channels and let calcium in
- this calcium can open RyR channels on SR, can also open VGCCs
Cross bridge cycling in smooth muscle
- calcium binds/activates calmodulin
- calmoduling activates MLCK
- MLCK will phosphorylate myosin whihc increases ATPase activity
- cross bridge cycling proceeded as in skeletal muscle as long as myosin is phosphorylated
What is myosin de phosphorylates by in smooth muscle
Myosin phosphatase
Cross bridging in smooth muscle simplified
Ca2+-calmodulin-MLCK-myosin phosphorylated
How does smooth muscle relax?
Dephosphorylation of myosin by myosin phosphatase
- occurs when MLCK is no longer active, requires low ICF Ca2+
- reduces ATPase activity and actin affinity
How does smooth muscle contract?
Either physically or tonically
Phasic contractions in smooth muscle
Are like skeletal muscle
-single spike of Ca2+, single contraction, and relaxation
Tonic contractions in smooth muscle
- signed Ca2+ spike but maintinaed force
- possible because of the ‘latch state” of smooth muscle myosin
- low metabolic demand
What is latch state in smooth muscle
- for myosin to let go it has to bind ATP
- unphosphorylatd mysoin has low affinity for ATP
- if it dephosphorylates while still attached to actin, it is slow to release because it is unlikely to bind ATP
What does latch state of smooth muscle allow for
Retina muscle tone to be generated at a much lower metabolic cost
Why is smooth muscle not striated
No sarcomere
Is the cycling of cross bridges slower or faster in smooth muscle compared to striated?
MUCH slower
Length of contractions in smooth compared to striated
Longer
What type of muscle can “latch”
Smooth
What is the metabolic demand on smooth muscle compared to striated
Lower
What causes the release of ca2+ in smooth muscle
Extracellular calcium
What kind of junctions do smooth muscle have
Gap
What is smooth muscle activated by
Circulating hormones or NT
Can you overstretched smooth muscle?
Not really because they don’t have sarcomeres
Length tension relationship of smooth muscle
Given time to accommodate, it will generate maximum force at any length
-same maximal force at all lengths because always have myosin/actin lineup
Force velocity relationship of smooth muscle
Increased load increases Ca2+ flux, increases MLCK activation, so it occurs stronger and faster
- velocity of contraction increases with % of myosin phosphorylated
- % phosphorylated increases with load
What does force velocity relationship of smooth muscle depend on
Phosphorylation of calcium
Muscles that need ECF Ca2+
- cardiac (always) and smooth (depends)
- hypercalcemia (stronger)
- hypocalcemia (weaker)
How does ECF calcium alter cell excitability (AP)
By changing threshold of Na(v)
-this is one instance where presence of Na will affect depolarization
Hypercalcemia in smooth muscle and cardiac muscle
Threshold more negative
- less excitable
- Ca2+ likes to keep Na+ channels closed
- contractions strong, but harder to have one
Hypocalcemia in smooth and cardiac muscle
Threshold less negative
- more excitable
- easy for muscle to contract but it is a weaker contraction
- test for it by flicking face and seeing if the muscles twitch
What would you expect to occur to strength of skeletal muscle contraction in the setting of hypercalcemia
Nothing
What would you expect to occur to strength of smooth muscle contraction in the setting of hypercalcemia
Stronger
Shape of cardiac muscle cells
Short, Y-shaped, chunky cell
What is responsible for the fact that the cardiac muscle contracts as one muscle?
Gap junctions at intercalated disks
-intrinsic muscle
Are APs longer or shorter in cardiac muscle
Longer
T-tubules in cardiac muscle
Fewer, but larger
Metabolism of cardiac cells
Fatigue resistance, more mitochondria, highly metabolic
Proximity of DHPR and RyR in cardiac muscle
Not close, must have extracellular calcium
Sarcolemmal calcium pumps in cardiac muscle
There are more of them (NCX and SERCA)
Resting membrane potential of cardiac muscle cells
Slightly lower
-there’s more K+ channels here, that’s why
How many phases are in a cardiac muscle action potential
4
Phase 4 of cardiac AP
RMP same as other excitable cells
-K+ leak channels (iK1)
Phase 0 of cardiac muscle AP
Upstroke Na(v) channels open
Phase 1 of cardiac muscle AP
Early repolarization
K+ channels i(t0)
Phase 2 of cardiac muscle AP
***
Plateau
- L-type Ca2+ channels and SR dump
- really long because of all of the calcium that moves
- reduces arrhythmia and tetanus
- needs to fully contract, and fully relax, not go into tetanus, this is why is needs to be this long
Phase 3 of cardiac muscle AP
Late repolarization
-K+ channels i(K)
Absolute refractory period of cardiac muscle (ARP)
Much longer
- this prevents tetany
- calcium open for a very long time
- ECF ca2+ is required to open RyR channels on SR, occurs during phase 1 and 2
Effective refractory period of cardiac muscle AP
- no conducted potential can generate AP (AP will fire nut not go anywhere)
- can get AP but not from normal source (such as electrodes)
Why do doctors want to lengthen the cardiac effective refractory period?
If you lengthen it, it treats arrhythmia. Do it by using K+ channel blockers
Relative refractory period (RRP) in cardiac AP
AP can fire if a greater than normal stimulus is provided
-will have shortened plateau
Supra normal period (SNP) in cardiac AP
Cell is more excitable than normal. Has yet to reach full RMP
Cardiac muscle mechanical
-contains sarcomeres and cross bridge cycling occurs as in skeletal muscle
Force generation in cardiac muscle compared to skeletal
Very slow
- different mysoin isoform, lower ATPase activity
- cardiac muscle needs to fully contract every time (100%), skeletal muscle has to be repeatedly stimulated
How do you increase force generation in cardiac muscle
Increasing calcium flow and sensitivity
What relationship is muy importante in cardiac muscle
Length tension relationship
Length tension relationship in cardiac muscle
Resting length is much shorter than optical length
- heart can generate more force when preload is increased
- it can stretch more than normal which causes much more force
What is the length-tension relationship in cardia muscle called
Frank starling law
Frank starling law
Length tension relationship in cardiac muscle
-heart can generate more force when preload is increased
What are cardiac pacemakers
Specialized cells in heart
- electrical conduction system
- SA node is primary
- no SR
RMP in cardiac pacemakers
Have an unstable RMP, the line is slanted, not straight
How do cardiac pacemakers depolarize
At a set rate
What is the basis of heart rate
Cardiac pacemakers
What phases of cardiac AP does the pacemakers have
4,0,3
Phase 4 AP in cardiac pacemakers
- unstable RMP
- i(K) channels slowly close, depolarization
- I(h) (funny channels, i(f)) channels open, Na+ channel, depolarize
- I(ca)T opens, more depolarization
What is the funny channel
A Na+ channel on the cardiac pacemaker that opens during phase 4 AP. Unstable RMP because this channel opens up
What is the funny channel activated by
Repolarization
Phase 0 cardiac pacemakers AP
Firing of AP
- I(ca)L opens
- depolarize
Phase 3 of AP in cardiac pacemakers
Repolarization
-i(K) channels open
PNS synapses of SA node
- M2 receptors (Gi)
- increase i(K) flow (hyperpolarize)
- decrease I(h) flow (funny) reduce slope, takes longer to depolarize
- decrease Ca2+ flow (harder to depolarize)
What is the total effect of PNS synapses of SA node
Make slow of phase 4 flatter
SNS synapses of SA node
Opposite PNS
- B1 receptors (Gs)
- increase I(h) flow (steeper slope) funny
- increase Ca2+ flow
What would you expect to happen to SA node depolarization rate (Phase 4) during hypernatremia?
Faster
-funny current open, allows Na+ in
Everywhere, Na+ doesn’t effect RMP
