Lecture 34 Flashcards
What is myofilament?
filamentous cytoplasmic organelle which gives the tissue its contractile property
3 types of striated muscle
skeletal, visceral, cardiac
Skeletal and visceral are voluntary, striated muscle. Where can they be found?
Skeletal : somatic/body wall
Visceral : soft tissue origin : tongue, pharynx, larynx, diaphragm, upper esophagus
What does syncytium mean?
multinucleated cell
Describe skeletal muscle development
- Mesenchymal cells differentiate into myoblsats which begin to form aggregates and line up into tube.
- Myotubes lengthen by incorporating additional myoblast by cell fusion
- Then, myofilaments appear, but nuclei are still centralized. As muscle fibers develop, cross-striated appearance is shown and nuclei are pushed peripherally.
- At last, muscle fibers are now thick and mature, consisting of alternate thick and thin myofilaments grouped into longitudinal bundles as myofibrils with nuclei located at periphery.
What is another name for skeletal muscle cell? (2)
myocyte or muscle fiber
What is satellite cells
formed from other myogenic stem cells, it is myoblast in connective tissue that can regenerate into myocyte.
3 organization of skeletal muscle
endomysium, perimysium, epimysium
what is endomysium?
a delicate layer of reticular fiber that surrounds individual muscle fiber
- contain small blood vessels and very fine neuronal branches
Perimysium
Groups of skeletal myocytes in fascicle or bundle. Each fascicle is surrounded by a layer of connective tissue
- Contain larger blood vessel and nerves
*
What is fascicles
functional unit of muscle fibers that work together
Epimysium
dense connective tissue sheath which encases multiple fascicles to form the total muscle
- contains major blood vessels and nerves
- essential for force transduction
- continues with tendon to attach muscle at the myotendinous junction
What is sarcolemma?
Plasma membrane of muscle fiber
Difference between type 1, type 2A, type 2B fibers
type 1 : slow oxidative fibers (marathoners)
- burn glucose and fatty acids
- small, red full of mitochondria, large amounts of myoglobin and cytochrome complexes.
- great resistance to fatigue
Type 2A : Fast twitch oxidative
Type 2B : Fast glycolytic (sprinter)
- burn glycogen and glucose
- large fibers, light pink
- contain less myoglobin, fewer mitochondria than type I and type IIA
- Fatigue prone
Difference between myofibrils and myofilaments
Myofibrils are specialized organelles composed of cytoskeletal elements (banded structure that extend length of the cell)
Myofibrils are made up of myofilaments, which are contractile elements.
- There are two types of myofilaments : Thick and thin with accessory proteins
Which structure is responsible for dark and light bands which accounts for cross striations of all striated muscle?
Thick and thin myofilaments
Define A, I bands, Z line, H band, M line
A : Dark I : Light Z : median dark of I H band : median lighter part of A M : middle line of H
What is sarcomere
functional unit of myofibril and basic unit of contraction, defined as segment of myofibril between two adjacent Z line
What is Thick filament made up of
MyosinII
What is thin filament made upof
actin
When stretched or contracted which part of myofilament change?
When stretched, Thin filament (I) would be stretched, moving away from A , so no overlapping, H increase
When contracted, I would move toward H band getting shorter , so more overlapping, and H decrease
*A never change
Structure of thin filament ( actin) (its synthesis)
- G-actin polymerize forming F-actin
- F-actin surrounded by tropomyosin which stabilize it.
- Troponin complex is attached to filament
- Troponin C : binds calcium
- Troponin T : binds to tropomyosin and anchors troponin complex
- Troponin I : Bind to actin, and inhibits actin-myosin interaction - Tropomodulin is attached and caps ‘-‘ end, regulating length of actin filament.
Structure of thick filaments
myosin II are aggregated tail tot ail to form thick filaments.
Cellular event leading to contraction
- Nerve impulse arrives at neuromuscular junction
- Release of acetylcholine into synaptic cleft, causing depolarization of sarcolemma
- Voltage-gated Na channels open and Na enters cell
- Depolarization of T-tubules
- Ca channel is activated, and Ca rapidly released from SR
- Ca binds to troponin C, causing contraction cycle to initate
- Ca returns to terminal cisternae
Myomesin & C-protein
myosin-binding protein that aligns thick filaments at M line
* C-protein is associated with M line and important for assembly and stabilization of thick filaments.
Titin
Spring-like protein that keeps thick filaments centered between the two Z lines of sarcomere and prevents excessive stretching
Nebulin
helps anchor thin filaments at Z line and regulates length of thin filaments during development
A-actinin
actin binding protein that bundles and helps stabilize thin filaments at Z-line
Desmin
Surrounds the sarcomere at Z line attaching them to one another and to the sarcolemma
dystrophin
rod-shaped cytoskeletal protein which links to ECM proteins laminin & agrin found in the external lamina of myocyte
With which proteins does dystrophin form a complex (2)
- Dystroglycan : link dystrophin and laminin of ECM
- Sarcoglycan : associated with membrane dystroglycans
* If sarcoglycan is impaired, it leads to Limb Girdle Dystrophy
Relationship between muscular dystrophy and dystrophin
The disease is attributed to mutations of single genes encoding several proteins of the dystrophin-glycoprotein complex (dystrophin + dystroglycans + sarcoglycans)
Difference between Ducheene muscular dystrophy and congenital muscular dystr ophy
DMD is mutation of gene that codes dystrophin
While congenital muscular dystrophy is a group of muscular dystrophy associated with ECM component (laminin)
Where are Sarcoplasmic reticulum and T-tubule found in myofibril?
Triad (1 tubule + 2 terminal cisternae) is located at A-I junction. And SR forms a network around the myofibril, extending from one A-I junction to the next A-I.
What is motor unit?
One neuron will innervate multiple muscle fibers which is called motor unit
*All muscles within a motor unit are of the same type (Either I, IIA, IIb)
Describe neuromuscular junction
- Presynaptic membrane of motor nerve contain synaptic vesicles that contain acetylcholine
- Synaptic cleft is where Ach is released
- At post synaptic membrane, there are junctional folds (folds at membrane of muscle fiber) with acetylcholine receptor
* NMJ is covered by Schwann cell external lamina
What is muscle spindle?
It is sensory innervation to muscles, containing modified muscle fibers(intrafusal muscle fibers) or spindle cells
- encapsulated sensory receptors that has specialized stretch receptor located in muscle belly.
It senses changes in muscle length or stretch
Golgi tendon organ
It is sensory innervation at myotendinous junction, which has encapsulated proprioceptor. It senses tension in the muscle.
* it is sensory component of Golgi tendon reflex.
Proprioreceptor
Sensory receptor that detects change in position and movement of body (e.g. golgi tendon organ at myotendinous junction)
Myasthenia Gravis (cause and manifestation)
Autoimmune disease which affects neuromuscular junction.
- Caused by acetylcholine receptor antibodies, which block and attack Ach receptors in postsynaptic membrane, leading to fewer Ach receptors
(Have shallower subjunctional folds and wider synaptic cleft)
- Results in fluctuating weakness and fatigue of skeletal muscle; ocular bulbar, limb and respiratory muscles affected
Characteristics of cardiac muscle (comparing to skeletal muscle) (7)
- striated and same arrangement of contractile filaments (actin & myosin) as skeletal muscle
- Cardiac myocytes are branched unlike SK muscle)
- Have intercalated discs that connect two cardiac muscles
- Have central nuclei
- In cross-section, nuclei appears to be enclosed by sarcoplasm.
- have large mitochondria and glycogen stores
- have granules of diuretic hormones (eg. atrial natriuretic peptide & brain natriuretic peptide)
- only for atrial cardiac muscle cells
- Its perinuclear region is free of myofibrils and contain organelles)
Role of atrial natriuretic factor (ANF) and brain natriuretic factor (BNF) (3)
- Inhibit renin secretion by kidney
- inhibit aldosterone secretion by adrenal gland)
- inhibit contractions of vascular smooth muscle
Difference of SR and T-tubule between Skeletal and cardiac muscle
Cardiac muscle
- SR extend from Z line to Z line
- Diad : 1 T-tubule + 1 terminal cisternae at Z line
- T-tubule is located at Z line (in SKM, its at A-I junction)
- Cardiac muscle has less developed SR than skeletal muscle.
Two types of intercalated disc
Transverse (right angle to myofibril)
Longitudinal or lateral (parallel to myofibril)
What kind of cell junction does traversal intercalated disc contain?
Fascia adherens (adhering junction) - major structural element which serves as attachment site for thin filaments in terminal sarcomeres. It binds cardiac muscle cells at their ends.
Maculae adherens (Desmosome)
- reinforcing fascia adherence, it binds individual muscle cells to each other.
- preventing their separation during contraction cycles
What kind of cell junction does Lateral intercalated disc contain?
Gap junction (communicating junction) - area subjected to least stress, important to spread contractile depolarization
Maculae adherens (desmosome) - preventing their separation during contraction cycles
What is purkinje fibers in cardiac muscle?
large, modified muscle cells located in subendocardial connective tissue
Role of purkinje fibers
specialized to conduct impulses of A-V bundle and allow synchronization of ventricular contraction
Staining of purkinje fibers
Has few myofibrils, and large amount of glycogen, thus staining is pale.
- Contain abundant mitochondria
Shape of smooth muscle cells
elongated, fusiform cells (spindle shaped), organized into bundles or sheets
- No cross-striations
- One central nucleus
How are smooth muscles connected?
They are interconnected with gap junctions (or nexus)
- provide communication link to regulate contraction of entire bundle or sheet
Structure of smooth muscle
- well developed rER and golgi and mitochondria
- dense bodies (contraction apparatus)
- pinocytotic vesicles
What does smooth muscle synthesize and secrete?
Type IV& III collagen fibers Elastin Proteoglycan Multi-adhesive glycoproteins * Vascular and uterine SM also secrete large amount of type I collagen and elastin
What is thin filaments of smooth muscle made up of?
Actin, tropomyosin, caldesmon and calponin
* Caldesmon and calponin bind to actin proteins blocking the myosin binding site.
What is dense bodies of smooth muscle?
Analogs of Z-line in striated muscle
Containing alpha actinin, it attach thin and intermediate filaments (vimentin, desmin).
- distributed throughout the sarcoplasm in a network of intermediate filaments
What is Myosin light chain kinase (MLCK) of smooth muscle
one of accessory protein that initiates contraction
- activated Ca-calmodulin complex
What is analogous structure of T-tubule in smooth muscle?
Caveolae which is invagination of cell membrane, SR and cytoplasmic vesicles
Describe smooth muscle contraction
- Hormone binds to receptor, which opens voltage-gated Ca channel as well as SR Ca pool. Thus, Ca conc. increase.
- Ca binds to calmodulin forming Ca-calmodulin complex
- Ca-calmodulin complex binds MLCK.
- MLCK phosphorylates regulatory light chain of myosin.
- This activates actin-binding site of myosin head and attaches to actin.
- Myosin and actin filaments form a crisscross lattice.
- Actin (thin) filaments are anchored to cytoplasmic and membrane dense bodies, which are than associated with small and intermediate filaments (such as vimentin and desmin)
- During contraction, thin filaments slide past the thick filaments. Actin-myosin shortening pull on the dense bodies, pulling ends toward the center.
- So cell adopts a globular shape and nucleus adopts “corkscrew” shape.
3 ways of regulation of smooth muscle contraction
- Mechanical
- passive stretching of vascular smooth muscle activates myogenic reflex - Electrical depolarization
- neural stimulation leading to release of Ach and NE - Chemical
- angiotensin II, vasopressin, thromboxane A2 (USE IP3 pathway)
Hypertrophy in skeletal, cardiac and smooth muscle
Which is possible?
Hypertrophy in skeletal and smooth muscle is possible, but cardiac hypertrophy is pathological (hypertensive cardiomyopathy)
Hyperplasia in skeletal, cardiac and smooth muscle
Which is possible?
Hyperplasia in skeletal and cardiac is not possible
hyperplasia of Smooth muscle of uterus possiblr during menstrual cycle or pregnancy.
Also, hyperplasia of SM of blood vessel possible due to hypertensive conditions.
Response to injury by skeletal muscle
Satellite cells are responsible for skeletal muscle regeneration, but limited capacity.
Response to injury by cardiac muscle
No regenerative capacity
After death of cardiac muscle cells, tissue is replaced with fibrous connective tissue, losing cardiac function.
Response to injury by smooth muscle
SM of blood vessel divide regularly differentiating from mesenchymal stem cells in the adventitia or from division and differentiation of endothelial cells following vascular injury.
