Lecture 34: Muscle Flashcards
Cellular Events leading to Muscle Contraction
1) Nerve impulse arrives at the neuromuscular junction
2) Acetylcholine –> synaptic cleft = depolarization of sarcolemma
3) Na+ channels open, Na+ enters cell = depolarization spreads to T Tubules
4) Ca2+ release channels activated, it releases from sacroplasmic reticulum
5) Ca2+ Bins to TnC (of troponin complex)
6) Contraction cycle initiated and Ca2+ returns to terminal cisternae
Actinomyocin cross-bridge cycle
1) Attachment: Myosin head binds to actin = rigor conformation (No ATP)
2) Release: ATP binds to mysosin head (changes conformation of actin = doesn’t want to bind to myosin) myosin uncouples from thin filament
3) Bending: ATP hydrolysis = conformational change and movement of myosin head
4) Force generation: Myosin binds weakly to new binding site on adjacent actin, causing binding affinity to increase between myosin head and actin
POWER STROKE: Myosin gains force and moves to original position, moving thin filaments = release of inorganic phosphate
5) Reattachment: Myosin head binds tightly to actin
Muscle Contraction
Sliding Filament Hypothesis of Huxley:
-Changes in the amount of overlap between thick and thin filaments allow for contraction and relaxation of muscle fibers
Sliding Filament Hypothesis of Huxley:
-Actin and myosin slide past one another (make and break attachments) = increased amount of overlap
-A band = constant
-I and H = decrease
z lines = drawn closer to the ends of the A band
Skeletal Muscle
Smooth Muscle
Cardiac Muscle
Skeletal Muscle:
- Striated
- Voluntary
- Somatic/ body wall
Visceral: -Striated -Involuntary -Soft tissue origin. Tongue, pharynx, larynx, diaphragm and upper esophagus
Cardiac Muscle:
- Striated
- Involuntary
- Heart
Smooth Muscle:
- Non-striated
- Involuntary
- Walls of visceral organs. Stomach, gut tube
- Corkscrew nucleus
Skeletal muscle development
Mesenchymal cells –> myoblasts –> myocytes
-Skeletal myocyte = muscle fiber
Skeletal muscle organization
Epimysium- E:
- Dense connective tissue
- Contains major blood vessels and nerves
Perimysium- P:
- Groups of skeletal myocytes/fibers form a fascicle
- Contains larger blood vessels and nerves
Endomysium- En:
- layer of reticular fibers that surrounds individual muscle fiber (myocyte)
- Contains small blood vessels and nerves
Skeletal Muscle Organization:
Myofibril
Myofibrils:
-Banded structures which extend the length of the cell
Microfilaments:
- Contractile elements of myofibrils (thick and thin)
- Arrangement of filaments creates dark and light bands which accounts for the cross striations characteristic of all striated muscle
Skeletal muscle:
Sarcomere
-The functional unit of the myofibril and
the basic unit of contraction
-Myosin (thick) filaments
-Actin (thin) filaments
(Both used for contraction of skeletal muscle)
- Darker areas= overlapping Actin and Myosin filaments
- Lighter areas= Actin filaments
Structure of myofilaments
Thin and thick filaments
Thin Filaments: -Actin -Tropomyosin: -Tropomodulin: Regulates length of actin -Troponin complex: • troponin-C (TnC) binds calcium • troponin-T (TnT) binds to tropomyosin and anchors troponin complex • troponin-I (TnI) inhibits actin-myosin interaction
Thick Filaments:
-Myosin II: Tail to tail formation= thick myosin filaments
Accessory proteins of myofilaments
Myomesin and C-protein:
-Myosin binding protein that aligns thick filaments at M line
Myosin binding protein C:
-Associated with the M line and important for the assembly and stabilization of the thick filament
Titin
-Spring like protein→ keeps thick filament centered between two the Z lines of the sarcomere and prevents excessive stretching
Nebulin
-helps anchor thin filaments at Z line and regulates length of thin filaments during development
Α - actinin:
-Actin binding protein that bundles and helps stabilize thin filaments at Z line
Desmin: Surrounds the sarcomere at Z lines attaching them to one another and to the sarcolemma
Dystrophin and Dystrophin-Associated proteins
1) What is it
2) What does it form
3) Clinical correlations
1) Dystrophin = rod-shaped cytoskeletal protein, links to ECM proteins laminin and agrin in external lamina of myocyte
CLINICAL CORRELATE: Duchenne and Becker’s Muscular Dystrophy
2) Forms a complex of two groups of transmembrane proteins
- Dystroglycans = links dystrophin and laminin of the ECM
- Sacroglycan = associated with membrane dystroglycans
- CLINICAL CORRELATE: Limb Gridle associated dystrophy
-CLINICAL CORRELATE: Muscular Dystrophy, also associated with ECM components
Structural requirements for contraction
1) Myofibril
2) Sarcoplasmic reticulum (SER)
3) Transverse tubules
4) Mitochondria
Neuromuscular Junction
Structure
1) Presynaptic membrane
2) Synaptic cleft (SnC)
3) Post synaptic membrane (of the muscle):
4) Schwann cell
Motor Innervation- Neuromuscular Junction
- Covered by external lamina
- Contact between the terminal branches of an axon and a muscle fiber
- Axons branch as they near the muscle and give rise to twigs that end on individual muscle fibers = motor units
Muscle contraction
-1 Neuromuscular junction per muscle fibers
Neuromuscular Junction
Structure
1) Presynaptic membrane
- Synaptic vesicles (SV) contain acetylcholine can be observed
2) Synaptic cleft (SnC)
- Where acetylcholine is released
3) Post synaptic membrane (of the muscle):
- Junctional folds (JF) w/ acetylcholine receptors
4) Covered with Schwann cell external lamina
Cardiac Muscle
- Cardiac myocytes are branched and striated
- One or two centrally-placed nuclei
- Numerous large mitochondria & glycogen stores
- Intercalated discs ID→ dense staining cross-bands
Myasthenia Gravis
-Autoimmune disease which affects neuromuscular junction ( NMJ)
- Common cause:
- Acetylcholine (Ach) receptorantibodies, which block and attack ACh receptors in the postsynaptic membrane
Symptoms:
- Drooping eyelids
- Double vision
- Difficulty swallowing
- Fluctuating weakness and fatigue of skeletal muscles
- Ocular, bulbar, limb, and respiratory muscles = affected
Cardiac Muscle
Intercalated disc parts
- Attachment sites between adjacent cardiac myocytes
- Mitochondrial abundant due to metabolic demands
Transversely parts (T): right angle to the myofibril
1) (FA)Fascia adherens (adhering junctions)
-Serves as attachment site for thin filaments
in terminal sarcomeres
2) (MA) Maculae adherentes (desmosomes)
- Bind muscle cells to each other
Longitudinal or lateral parts (L): parallel to myofibril:
1) (GJ)Gap junctions (communicating junctions)
2) Maculae adherentes
Purkinje fibers
- Large, modified muscle cells located just deep to the endocardium in the subendocardial connective tissue
- allows synchronization of ventricular contraction
- Pale staining
- Abundant in mitochondria
Smooth muscle
-Usually arranged in sheets around the lumen of
hollow organs
-Central nucleus
Smooth muscle
Structure
1) Gap junctions or nexus
2) Sarcoplasmic reticulum
3) Pinocytotic vesicles
4) Dense bodies
Smooth muscle cells secrete connective tissue matrix
- Synthesizes IV and III collagen
- Elastin, proteoglycans, multi-adhesive glycoproteins
Smooth Muscle Contractile Apparatus
Thick filaments
-Myosin II scattered through sacroplasm
Thin filaments
- Actin
- Tropomyosin
- Caldesmon and Calponin (binds to actin blocking myosin binding sit)
Accessory proteins
- Myosin light chain kinase- initiates contraction
- Alpha-actinin
- Calmodulin- Ca2+ bining protein
- Ca2+- Calmodulin complex binds/activates MLCK
Dense bodies
- Attach thin and intermediate filaments
- Desmins
- Vascular smooth muscles contains vimentins & desmins
No T Tubule System
Smooth Muscle Contractile Apparatus
Thick filaments
-Myosin II scattered through sacroplasm
Thin filaments
- Actin
- Tropomyosin
- Caldesmon and Calponin (binds to actin blocking myosin binding sit)
Accessory proteins
- Myosin light chain kinase- initiates contraction
- Alpha-actinin
- Calmodulin- Ca2+ binding protein
- Ca2+- Calmodulin complex binds/activates MLCK
Dense bodies
- Attach thin and intermediate filaments
- Desmins
- Vascular smooth muscles contains vimentins & desmins
No T Tubule System
Smooth muscle contraction
- Regulated by Ca2+- calmodulin-MLCK system
1) Increase in Ca2+ [ ]
2) Ca2+ binds to calmodulin forming the Ca2+-calmodulin complex
3) Ca2+-calmodulin complex bind MLCK
4) MLCK phosphorylates regulatory light chain of myosin
5) Actin-binding site of myosin head is activated and attaches to actin
