Muscle Flashcards

1
Q

Thick filament of the sarcomere

A

Myosin II molecules assemble via their tail regions, with their heads projecting to the outside of the filament. Note the central bare zone, which is free of head domains.

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2
Q

Excitation-Contraction Coupling

A

It is different in skeletal, cardiac, and smooth muscle.

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3
Q

Intercalated Disks

A

Individual cardiac myocytes are connected by “intercalated discs”. These contain desmosomes and other adherent junctions which hold the cells firmly together. Gap junctions are also present, forming “electrical synapses” that allow calcium to pass from cell to cell as a single wave.

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4
Q

myosin II

A

Form of myosin which generates contractile force in muscle

A myosin II molecule is composed of two heavy chains (green) and four light chains (blue). The light chains are of two distinct types, and one copy of each type is present on each myosin head. The α helices of two heavy chain molecules wrap around each other to form a coiled-coil, driven by the association of regularly spaced hydrophobic amino acids. The coiled-coil arrangement makes an extended rod in solution, and this part of the molecule is called the tail. Each myosin head binds and hydrolyzes ATP during muscle contraction.

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5
Q

Activation of smooth muscle contraction

A

Smooth muscle contraction is also triggered by calcium, but in this case it is independent of troponin (which is not present in smooth muscle).

The cycle starts with a pulse of Ca2+ that enters the smooth muscle cell and activates calcium-induced calcium release from the SR. This release of calcium leads to binding of Ca2+ to calmodulin, which in turn activates myosin light chain kinase. MLCK phosphorylates the light chain of myosin, leading to a conformational change in the myosin head and the activation of myosin ATPase and force generation.

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6
Q

Cardiac myocytes

A

Contain more mitochondria than skeletal muscle cells to supply the heart with enough ATP for its continuous workload

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7
Q

Smooth muscle organization in tissues

A

In hollow and tubular organs, smooth muscle is often arranged in two (or more) layers that are perpendicular to each other. This is most evident in the GI tract, where the smooth muscle is arranged into an inner circular layer (closer to the epithelium) and an outer longitudinal layer (closer to the serosa/peritoneum).

The circular layer regulates the diameter of the tube (contraction will constrict it), allowing regulation of flow and emptying, while contraction of the longitudinal layer will push things along (peristalsis)

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8
Q

Epimysium

A

A dense connective tissue layer that encloses the entire muscle, and is continuous with the tendon that attaches the muscle to the bone.

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9
Q

Synchronization of muscle contraction

A

An action potential (AP) initiated at the neuromuscular junction is normally the first event in E-C coupling. The AP rapidly propagates over the sarcolemma and into the T-tubules. When the T-tubule is depolarized, the voltage sensors (⊕) in the DHPRs move and open the RyRs, thus permitting Ca2+ to flow out of the SR into the cytosol to trigger contraction.

Once the impulse for muscle contraction (i.e., the action potential) is no longer present, cytoplasmic calcium concentrations must return to baseline to prevent further contraction. This is accomplished through the action of the SERCA (sarco/endoplasmic reticulum Ca 2+-ATPase) pump, which is located in the membrane of the SR and actively transports calcium from the cytoplasm back into the SR, using energy generated from ATP hydrolysis.

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10
Q

Muscle striation

A
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11
Q

Muscle fiber cross section

A
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12
Q
A
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13
Q

Rigor mortis

A

Since ATP is required to release myosin from actin, after you die and your muscles run out of ATP, myosin filaments will remain bound to actin and locked in their contracted conformation.

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14
Q

Type-Differential muscle fiber staining

A
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15
Q

The cardiac conduction system

A

The sinoatrial node (SAN) is known as the heart’s pacemaker. It is located within the wall of the right atrium (RA) and normally generates electrical impulses that are carried by special conducting tissue to the atrioventricular node (AVN). Upon reaching the AVN, located between the atria and ventricles, the electrical impulse is relayed down conducting tissue (bundle of His) that branches into pathways that supply the right and left ventricles.

Purkinje fibers receive nerve impulses from the conduction system and disseminate the impulses within the myocardium itself, ensuring that the heart connects as a unit. They stain more intensely eosinophilic than myocytes because they contain relatively fewer mitochondria (as they are not contractile), and mitochondrial DNA imparts a relatively basophilic appearance.

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16
Q

Z lines

A

Flank the ends of each sarcomere. They are visible as single dark lines in the electron micrograph and present the attachment sites for actin (thin) filaments.

The actin filaments, where they don’t overlap with myosin, are visible as light bands. The darkest area (on either side of the center) is where the myosin (thick) filaments intercalate with the actin filaments. The lighter area in the center is the area with only myosin.

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17
Q

Actin-myosin contraction cycle

A

https://embryology.med.unsw.edu.au/embryology/index.php?title=File:Actin_myosin_crossbridge_3D_animation.gif

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18
Q

Cardiac Muscle

A

Nuclei are more centrally placed, rather than being pushed to the periphery of the fiber as in skeletal muscle.

The cells often branch rather than exclusively forming linear fibers (not well-visualized here).

Cells are connected by intercalated disks, shown by the green arrows in the image. These structures, which contain gap junctions and desmosomes, are necessary to allow the heart to beat as a unit.

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19
Q

sarcolemma

A

plasma membrane of muscle

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20
Q

Initiation of cardiac contraction

A

Cardiac cells express a different form of the ryanodine receptor than skeletal muscle, called RyR2. The RyR2 differs from the RyR1 expressed in muscle in that it does NOT directly interact with the DHPR.

When the membrane is depolarized, the DHPR will open will allow calcium to enter the cell. Calcium can then bind to specific binding sites on the RyR2, triggering it to open and release calcium from the sarcoplasmic reticulum into the sarcoplasm. This mechanism is called calcium-induced calcium release.

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21
Q

Cross-sectional cardiac muscle diagram

A
22
Q

Smooth muscle transmission EM

A

The nucleus (N) and cytoplasm (C) are labeled. In the cytoplasm near the nucleus (N) are mitochondria, glycogen particles, and Golgi complexes.

Several dense bodies (arrows) can be seen in the cytoplasm and at the cell membrane. Thin filaments and intermediate filaments both attach to the dense bodies. These function as the anchoring points for smooth muscle contraction.

23
Q

Skeletal muscle histomorphology

A
24
Q

Cardiac excitation-contraction-termination

A

The more calcium becomes available, the more RyR2 receptors will open. Importantly, because cardiac myocytes are connected by gap junctions, calcium will not only be able to activate contraction in one cell, but the calcium wave will be transmitted through gap junctions from one cardiomyocyte to another. This mechanism allows the whole heart to contract in a synchronous fashion. This also explains why there is less need of the SR to be in direct proximity to the T-tubules.

Termination of cardiac muscle contraction is accomplished through actively pumping Ca2+ out of the cytoplasm – both into the SR (80%, via the SERCA pump) and into the extracellular space (20%, via pumps in the plasma membrane called PMCA and NCX)

25
Q

Fascicle

A

A bundle of muscle fibers. Each fascicle (or bundle) is wrapped in another connective tissue layer called the perimysium.

26
Q

Myosin Light Chain Kinase

A

As in skeletal and cardiac muscle, myosin II is the “motor” that generates the force for contraction. The light chains are of two distinct types (regulatory and essential), and one copy of each type is present on each myosin head. In smooth muscle, regulation of contraction is at the level of myosin. Myosin is phosphorylated on the regulatory light chain by a kinase called myosin light chain kinase (MLCK). Regulatory light chain phosphorylation results in activation of the myosin heads for contraction.

27
Q

Muscle

A

A bundle of fascicles (which are itself bundles of muscle cells or myofibrils) surrounded by the epimysium

28
Q

Bicep/Tricep

A
29
Q

Type II fibers

A

“Fast twitch” fibers

Rely more on anaerobic (glycolytic) metabolism, which allows them to continue to generate force under oxygen-limiting conditions, but at the cost of reduced efficiency and increased fatigability.

There are two types of type II fibers, IIA (which have a bit more oxidative capacity) and IIB (which are almost entirely glycolytic).

Type IIB fibers stain for ATPase but NOT succinate dehydrogenase

30
Q

Type I fibers

A

Slow twitch” Fibers

Have many mitochondria and rely primarily on oxidative metabolism to maximize efficiency and allow for sustained contraction with minimal fatigue.

Type I fibers can be identified based on their staining for succinate dehydrogenase​.

Also carry more myoglobin to store oxygen.

31
Q

Myofibril

A

A bundle of sarcomeres (the individual unit of contraction). Each muscle fiber (cell) contains hundreds of myofibrils

32
Q

Muscle contraction continues until . . .

A

Contraction activity continues until Ca2+ ions are removed and the troponin–tropomyosin complex again covers the myosin-binding site

33
Q

Troponin and tropomyosin

A

Tropomyosin binds along the groove of the actin filament. The troponin complex is made up of three polypeptides (troponins T, I, and C) which are named for their tropomyosin, inhibitory, and calcium-binding activities, respectively.

In resting muscle, the troponin I-T complex pulls tropomyosin into a position that interferes with the binding of the myosin heads, preventing any force-generating contraction. When calcium levels increase, troponin C binds to calcium, and this causes troponin I to release its hold on actin. This alters the position of tropomyosin such that the myosin heads are able to bind and walk along the actin filaments.

34
Q

Neuromuscular Junction Contraction Cascade

A

T-tubules: Transverse tubules, Invaginations which go deep into the muscle and surround each myofibril.

35
Q

Smooth muscle contraction cartoon

A
36
Q

Muscle fiber

A

An individual muscle cell. Individual muscle fibers are elongated cells with multiple nuclei (note: the term for a cell with many nuclei sharing a common cytoplasm is a syncytium). Each fiber is surrounded by a very delicate layer called the endomysium, which includes an external lamina produced by the muscle fiber (and enclosing the satellite cells) and extracellular matrix produced by fibroblasts.

37
Q
A

Smooth muscle

Compared to skeletal and cardiac muscle, smooth muscle is relatively disorganized. The cells are elongated, with the nucleus centrally placed in the middle of the cell and the two ends diminishing to a small pointed end (“fusiform”).

38
Q
A

Skeletal muscle from the side

39
Q
A

Top right: smooth muscle

Bottom right: skeletal muscle

This is from the esophagus, one of the few places in the body where both may be seen in one section.

40
Q

Dystrophin

A
41
Q
A

Hypertrophic cardiomyopathy cardiac muscle

42
Q

RyR channels

A

RyR1 resides in the skeletal muscle sarcoplasmic reticulum membrane, where it is bound to the cell-membrane traversing and voltage sensing DHLR receptor. When DHLR picks up a depolarization event, RyR1 opens and allows Ca2+ out of the sarcoplasmic reticulum.

RyR2 resides in the cardiac muscle sarcoplasmic reticulum membrane, where it acts as a Ca2+-sensing Ca2+ channel and opens in response to increased calcium levels.

43
Q

Angina

A

Chest pain

44
Q

Which types of muscle are multinucleate?

A

Skeletal and cardiac, but NOT smooth.

45
Q

Why not just have large myofibrils instead of many small myofibrils?

A

Calcium diffusion!

Also, you can have a wide range of muscle contraction for each neuron firing (controling bicepts vs eye muscles).

46
Q

Muscular dystrophy

A

a family of inherited diseases that result in weakness and degeneration of skeletal muscle.

47
Q

Duschene’s Muscular Dystrophy

A

X-linked recessive dystrophy disorder caused by a loss of a dystrophin splice site which results in a frameshift mutation producing a fully nonfunctional product.

Effectively causes scar tissue formation within muscles due to inflammation. Loss of muscle function.

48
Q

Beckman’s Muscular Dystrophy

A

X-linked recessive mutation in a splice site in dystrophin resulting in a loss of several exons without frameshift. Produces a partially-functional product.

Loss of some muscle function.

49
Q

Hypertrophic cardiomyopathy

A

Conduction of purkinjee cells may be disrupted by buildup of connective tissue around them. Little can be done about this and it predisposes to arrhythmia and total loss of effective conduction.

May be caused by mutations in numerous genes involved in regularing muscle contraction.

50
Q

Nonsense-mediated decay

A

The Exon-Junction-Complex is left over after the premature termination codon. The ribosome may pick up on this during the pioneer round of translation. The ribosome recruits UPF1, 2, and 3, which marks the mRNA for degradation.

51
Q

RNA-like oligomer therapy

A

An RNA-like molecule complimentary to an exonal sequence for an exon one wishes to skip may be used to do so by blocking the binding of exon definition machinery (SR protein, etc.) It is important that this not BE RNA, otherwise it would activate RISC.