Skeletal/Cardiac/Smooth Muscle

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1. Classification of cardiac muscle
2. Classification of smooth muscle

1. involuntary striated
2. involuntary, not striated

Main similarity btwn cardiac and skeletal muscles?

Striated
-myofibril organization basically the same

1. How is a cardiac contraction initiated?
2. How is the rate of contraction controlled?

1. spontaneous depolarization of pacemaker cells
2. autonomic nervous system (vagus nerve)

7 major differences between cardiac and skeletal muscles:

Cardiac muscles exhibit:
1. cell junctions (intercalated disks)
2. larger t-tubules
3. SR small
4. extracellular Ca2+
5. Exchange Ca2+ out of cell during relaxation
6. lots of mitochondria (ox phosphorylation)
7. fiber orientation not parallel

1. What are intercalated disks?
2. two regions of the disk?

1. specialized junctions of cardiac muscle
2. -transverse (parallel to m-line) - adhering region
- lateral (parallel to myofibrils)- communicating region

1. Two junctional complexes in the transverse portion of intercalated disks:
2. Junctional complex of the lateral portion of intercalated disks

1. fascia adherens and desmosomes
2. gap junctions

1. Function of the fascia adherens?
2. Function of desmosomes?
3. Function of gap junctions?

1. anchoring for actin
2. links two myofibril bundles together
3. cell-cell communication

1. What is the "diad" of cardiac muscle cells?
2. How is this different from skeletal muscle cells?

1. large t-tubule + one small terminal cisternae
2. one small t-tubule btwn two large terminal cisternae

1. AP duration of skeletal muscles
2. AP duration of cardiac muscles
3. Three distinct phases of cardiac muscle AP

1. 4 ms
2. 200 ms
3. depolarization (Na+ in), plateau phase (Ca2+ in), repolarization (K+ out)

How is a spontaneous cardiac depolarization result in contraction?

depolarization -> Na+ in -> opens voltage-gated Ca2+ channels -> extracellular Ca2+ in -> activate Ca-sensitive Ca2+ channels on SR -> enough Ca2+ for contraction

1. What is the relationship btwn the amount of extracellular Ca2+ coming into a cardiac cell and the force of contraction?
2. How is Ca2+ removed during relaxation (3)?

1. linear
2. - some is pumped back to SR (ATPase)
- pumped to ECM (ATPase)
- transported to ECM while Na+ comes in (antiporter)

2 major requirements of cardiac muscle for non-fatigueable contraction:

1. tons of mitochondria
2. efficient O2 delivery
-75% extraction of blood oxygen

1. What is the axis of tension of cardiac cells?
2. rotational difference between one end of heart and midwall?
3. rotational difference from end to end?
4. Significance of this?

1. variable - allows heart to squeeze to pump blood
2. 90 degrees
3. full 180 degree turn
4. prevents wall from rupturing when contracting

1. Smooth muscle is found where? (3)
2. How can smooth muscles be arranged?

1. GI tract, resp tract, blood vessels
2. tubular - either in sheets or circular bands

1. How are smooth muscle cells structured?
2. What types of contraction are they capable of?
3. What is their non-contractile function?

1. tapered - fat body, thin ends
2. maintaining continuous contractions
3. like fibroblasts
- can divide mitotically (multipotent)
-can make elastin, collagen, GAGs, proteoglycans

1. Why aren't smooth muscles striated?
2. What is the appearance of smooth muscle cells when contracted?
3. What surrounds the sarcolemma of smooth muscle (2)?

1. thin and thick filaments are scattered
2. "pleated" - shortened and twisted
3. basal lamina and reticular connective tissue

1. Difference btwn smooth and skeletal muscle actin?
2. Difference btwn myosins?
3. role of intermediate filaments in smooth muscle?

1. doesn't have troponin
2. different light chains in neck region, tail region loops back and covers actin binding site on head region
3. scaffolds

1. What is the ratio of thin to thick filaments in smooth muscle?
2. Where is actin-myosin binding regulated in smooth muscle?
3. What are dense bodies?

1. more thin than thick
2. at myosin - tail region blocks binding site at head
3. anchoring point that serves as a z-line

1. Are there terminal cisternae in smooth muscle?
2. what are caveolae?

1. no
2. like t-tubules, but only indent into cell a little bit
-increases SA

1. is smooth muscle contraction all-or-none?
2. Does smooth muscle contain sarcomeres?
3. Is actin/myosin interaction the same in smooth muscle as other types?

1. no
2. no
3. yes

Steps from initiation to contraction of smooth muscle:

stimulation (many ways to do) -> Ca2+ in -> binds calmodulin -> binds to myosin light chain kinase -> ATP used -> phosphorylates myosin tail loop -> exposes actin-binding site on myosin -> myosin binds to actin

2 arrangements of smooth muscle innervation:

1. visceral smooth muscle
2. multi-unit smooth muscl

1. How is visceral smooth muscle organized/innervated?
2. function of visceral smooth muscle?
3. How are multi-unit smooth muscles innervated?

1. circular or lateral sheets - only few cells get innervation, impulse travels to rest through gap junctions
2. sustained, slow contractions of peristalsis
3. small bundles with lots of innervation -> rapid and precise contractions

1. How do autonomic axons innervate smooth muscles?
2. two NTs responsible for smooth muscle depolarization:

1. "en passant" - in passing
2. ACh, norepinephrine

1. Can skeletal muscle regenerate after injury?
2. Can cardiac cells regenerate after injury?
3. Can cardiac cells hypertrophy?
4. Are smooth muscles capable of hypertrophy?
5. Hyperplasia?

1. yes - satellite cells
2. no
3. yes
4. yes
5. yes

Two basic elements of muscle:

1. muscle cells (fibers) - contractile force
2. connective tissue - framework

3 functions of mucle:

1. External and internal movement
2. Posture
3. Heat generation

Structural requirements of muscle (4):

1. must generate tension (shorten 2/3 of its length)
2. attachment
3. control of contraction
4. repair after damage or injury

2 more names for a muscle cell

1. muscle fiber
2. myocyte

Hierarchy of muscle structure:

myofilaments (thin and thick) -> myofibrils -> muscle fiber -> fascicle -> muscle

1. What is a muscle fascicle?
2. what is the loose conn tissue surrounding cell fibers?
3. What are myofibrils?
4. What is the perimysium?
5. what is the epimysium?

1. group of muscle fibers
2. endomysium
3. structural units within the muscle cell sarcoplasm
4. surrounds fascicles
5. surrounds muscles (type I collagen)

Where are the capillaries located in muscles?

endomysium

1. Three types of muscle:
2. Which type lacks sarcomeres (striations)?
3. Which type is multinucleated?
4. Which type lacks cell junctions?
5. Which type is voluntary?
6. Which type is incapable of regenerating?
7. Which type can undergo mitosis?

1. skeletal, cardiac, smooth
2. smooth
3. skeletal
4. skeletal
5. skeletal
6. cardiac
7. smooth

1. Shape of skeletal muscles
2. muscle classification
3. Can it undergo mitosis?
4. Where are the nuclei?

1. long cylinders
2. voluntary striated
3. no
4. in periphery

1. Shape of cardiac muscles
2. muscle classification

1. branched fibers
2. involuntary striated

1. Shape of smooth muscle
2. muscle classification
3. cell junctions?
4. capable of division?

1. fusiform (cigar-shaped)
2. involuntary nonstriated
3. yes, gap junctions
4. yes

WHat are intercalated disks?

-gap junctions of cardiac muscle
- helps depolarization spread throughout

Specialized skeletal muscle cell components (5):

1. sarcolemma
2. sarcoplasm
3. sarcoplasmic reticulum
4. myofilaments
5. sarcosomes

1. What are sarcosomes?
2. What is stored in the sarcoplasmic reticulum?
3. What is a sarcolemma?

1. specialized mitochondria, near the I band of skeletal muscle
2. Ca2+
3. specialized t-tubules

What oxygen-carrying protein is found in skeletal muscle fibers?

myoglobin

3 types of skeletal muscles, with respect to their myoglobin content:

1. Red (type I)
2. Intermediate (Type II A)
3. White (Type II B)

1. Rank types of skeletal muscle by size
2. Which type has the most myoglobin?
3. Which type stores the most glycogen?
4. Which type contracts the fastest?
5. Which type is fatigued easily?
6. Which type is most aerobic?
7. Which type is anaerobic and aerobic?

1. red < intermediate < white
2. red
3. white
4. white
5. white
6. red
7. intermediate

1. The proportion of red, white, and intermediate skeletal fibers within a given muscle is _____
2. Power training would increase what?

1. fixed
2. white muscle cross sectional area

1. The dark region of overlapping actin and myosin
2. light band of only actin filaments
3. the band of only thick filaments
4. the line with myosin + crossbridges
5. anchor site of thin filaments of separate sarcomeres

1. A-band
2. I-band
3. H-band
4. M-line
5. Z-line

What is a sarcomere?

-functional unit of skeletal muscle fiber
- z-line to z-line

4 major proteins at the z-line:

1. z-line protein - anchoring protein
2. alpha-actinin - binds actin
3. Cap-z - caps (+) end of actin at the z-line
4. Titin - anchors myosin tails

Proteins associated with actin filaments (5)

1. cap-z - caps (+) end at z-line
2. tropomodulin - caps (-) end
3. tropomyosin - covers myosin binding sites on each G-actin
4. nebulin - runs the length of actin to keep straight
5. troponin - 3 binding subunits, regulated by calcium, bound to tropomyosin

3 subunits of troponin:

1. TnT - binds to tropomyosin
2. TnI - regulates availability of actin-myosin binding site on actin
3. TnC - binding site for calcium

What forms filamentous actin?

2 strands of G-actin

Myosin exists as a ______

dimer

1. Function of titin
2. Function of nebulin
3. Location of both?

1. anchors myosin
2. anchors actin
3. z-line

2 M-line proteins:

1. myomesin - holds myosin bundles apart to allow overlap of thin filaments
2. creatine kinase - converts ADP to ATP

What is C-protein in skeletal muscle?

- binds myosin strands together to make a filament

Three regions of a myosin monomer:

1. short head region (heavy meromyosin) with ATP site and actin site
2. short neck region (heavy meromyosin)
3. long tail region (light meromyosin)

3 important components of the head/neck region of myosin:

1. ATP binding site
2. Actin binding site
3. Flexible neck region for conformational change

Where are the 2 flexing points of myosin:

1. flex 1 = on neck, helps head reach out towards actin (proximity)
2. flex 2 = near head, hels lock onto actin and stroke

2 events that muscle contraction depends on:

1. Depolarization at NMJ
2. Release of Ca2+ from SR

1. Resting potential of a skeletal muscle?
2. Depolarized potential?

1. -90mV
2. +30 mV

1. What is the function of the sarcoplasmic reticulum?
2. What are the bulbous end feet of the sarcoplasmic reticulum?

1. Major Ca2+ reservoir, surrounds every myofibril
2. terminal cisternae

1. What are t-tubules?
2. What band junction does it invaginate?
3. What is its function?

1. invagination of sarcolemma into tubes
2. at junction of A and I bands
3. Rapid distribution of depolarization to all myofibrils

What makes up the "triad" of skeletal muscle cells?

A t-tubule sandwiched in between two terminal cisterna of the SR

1. Band that remains unchanged when muscle contracts
2. Bands that decrease in size when muscle contracts

1. The A band (region of entire myosin filament)
2. The I band (actin only) and H-zone (myosin without actin) decrease

1. T/F contraction of a muscle is an all-or-none event
2. Each thin filament is in association with __(#)__ thick filaments
3. Each thick filament is in association with __(#)__ thin filaments

1. true
2. 3
3. 6

5 major steps of skeletal muscle contraction:

1. AP from nerve fiber to motor end plate
2. Transmission of impulse through ACh to depolarize muscle
3. Release of Ca2+ from SR
4. Unmasking of myosin binding site on actin
5. Binding of myosin to actin -> power stroke

1. Somatic motor neurons are afferent or efferent?
2. Where do they stem from?
3. Does each muscle fiber receive neuronal contact?

1. efferent
2. ventral horn of spinal cord
3. yes

1. What is a motor unit?
2. What causes more precise motor movements?

1. one motor neuron + all of the muscle fibers it innervates
2. Motor units with fewer muscle cells per neuron

1. What is a motor end plate?
2. What is a primary synaptic cleft?
3. What are secondary synaptic clefts?

1. Specialized flatting of motor axon terminal to make a "contact" with muscle
2. gap from invagination of muscle cell, where motor end plate is
3. smaller enfoldings of sarcolemma that increase SA of "contact"

1. The NT at the NMJ?
2. What receptors are on the sarcolemmal membrane?

1. ACh
2. nACh receptors

How is an action potential transferred into a muscular depolarization?

ACh in vesicles -> to cleft -> bind to nACh receptors on sarcolemma -> open ligand-gated Na+channels -> local depolarization -> opens voltage-gated Na+ channels -> widespread depolarization

1. How long does muscle depolarization last?
2. What is the latent period?
3. When does contraction occur?

1. from t = 0-4 ms
2. from t = 4-10 ms, time btwn depolarization and contraction
3. from ~10 - ~100 ms

What is the problem with the classic story of voltage-induced Ca2+ release from the SR?

-IP3 = thought to appear after depolarization in t-tubules -> binds to Ca2+ channels of SR -> release of Ca2+
-problem: blocked IP3 and still got contraction

How does muscular depolarization cause Ca2+ release from SR?

depolarization down t-tubules -> activates DHPR receptor in sarcolemma -> causes twisting of DHPR -> conf change of its coupled protein, ryanodine -> opens ryanodine's Ca2+ channel -> Ca2+ out from SR

1. Does the muscle intracellular concentration of calcium change during depolarization?

No - just moves from SR to cytosol

What is the effect of Ca2+ being released from the SR?

Ca2+ binds to troponin at TnC -> lateral rotation of tropomyosin into the inner groove of the 2 actin helices -> myosin binding site of actin is uncovered

Steps of the power stroke cycle, beginning with actin and myosin being unattached

Unattached when ATP bound to myosin -> ATP hydrolyzes to ADP and Pi -> myosin cocks -> if Ca2+ attached to troponin, myosin binds to actin -> release of Pi -> ADP release -> power stroker -> ATP binds to detach myosin and actin

THe power stroke cycle can continue as long as: (2)

1. Ca2+ levels are maintained
2. ATP is available

What occurs in rigor mortis?

Die -> no ATP around to detach actin and myosin -> muscles stuck in the rigor state/complex

1. 2 major steps of muscle relaxation:
2. is this an active or passive process?

1. Ca2+ pumped back to SR, Ca2+ detached from troponin
2. Active - Ca2+ ATPase requires energy

How is calcium removed from the cytosol back to the SR of muscles?

Ca2+ ATPase of SR pumps it back to SR -> Ca2+ binds to calsequestrin in SR

3 major uses of ATP in muscle:

1. power stroke
2. breaks rigor complex
3. powers Ca2+ ATPase

1. What is an alternate mechanism of ATP regeneration in muscle?
2. Where does this occur in muscle?

1. Phosphocreatine + ADP -> ATP + creatine
2. at the m-line

1. What are muscle spindles?
2. Function:

1. Modified muscle cells, or intrafusal fibers
-contain few myofibrils
2. Stretch receptors - provide sensory feedback about the state of contraction
-greater # -> greater muscle control

2 types of intrafusal fibers:

1. nuclear bag fibers - long, thick, scattered nuclei
2. nuclear chain fibers - short, thin, nuclei in rows

2 types of afferent neuronal endings at intrafusal fibers:

1. annulospiral (primary) endings - wrap around intrafusal fibers
2. flower spray (secondary) endings - branches on nuclear chain fibers

How do muscle spindles relay info back to CNS?

muscle stretch -> nerve impulse -> info about state of contraction

1. What is the role of the protein dystrophin?
2. What is muscular dystrophy?

1. anchors actin to muscle cell membrane
2. X-linked disorder, mutation in dystrophin protein -> cell membrane destabilized -> ruptured during repeated contraction -> muscle cell loss -> death due to cardiac, resp muscle damage

1. What is myasthenia gravis?
2. How is it treated?

1. Autoimmune disorder - antibodies attack nACH receptors at NMJ -> decline in receptor # -> weak, fragile muscles
2. AChE inhibitors, immunosuppressants

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