Muscle I, II, & III Flashcards
Describe the sarcomere
-Functional unit of muscle, defined as the space from one Z-line (disc) to the next Z-line (disc)
Describe the organization of muscle from macroscopic to microscopic
muscle belly–>fascicle–>muscle fiber (single cell)–>myofibrils–>sarcomeres
Muscle belly = biceps brachii
Fascicle = bundle of muscle fibers
Muscle fibers (single cell) = collection of myofibrils
myofibrils = collection of sarcomers covered in their own sarcoplasmic reticulum
Describes the stages of skeletal muscle contraction
- Acetylcholine released from lower motor neurons binds nicotinic acetylcholine receptors on muscle cell (nicotinic AchR are ion channels).
- Influx of Na into myocyte causes an action potential in the myocyte.
- The action potential quickly moves down the plasma membrane of the muscle cell (sarcolemma) until it reaches a T-tubules.
- At the T-tubule, depolarization of sarcolemma causes a conformational change in the dihydropyridine receptor (DHPR).
- The conformational change in the DHPR allows Ca to flow through the rhyanodine receptor (RyR) from the sarcoplasmic reticulum into the cytoplasm.
(DHPR can be thought of like a cork, while the RyR can be thought of like a bottle stem. You pop the cork on the bottle, and that sweet, sweet contraction juice flows from the bottle stem into the maw of the myofibril).
- Ca diffuses a short distance through the cell before reaching the sarcomeres.
- At the sarcomeres, Ca binds to troponin (troponin C specifically)
- Binding of Ca to troponin C causes a conformational change in tropmyosin, revealing myosin binding sites on actin thin filaments
- When myosin binds actin, it’s in a high-energy (cocked) state. Release of ADP and Pi from the myosin head cause the myosin head to revert to a lower energy state, pulling on actin and causing contraction of the sarcomere.
- ATP binds to the empty binding site on myosin heads, causing the dissociation of myosin from actin.
- The cleavage of ATP into ADP and Pi provides the energy necessary for the myosin head to re-form the high-energy cocked state.
List some of the other important proteins in muscle besides myosin and actin
- Dystrophin: huge protein important for coupling cortical actin cytoskeleton to the extracellular matrix.
- Titin: as its name implies, titin is the biggest protein in the human body. It functions to link myosin filaments to the Z disc. The purpose of this is thought to be keeping myosin filaments centered in the sarcomere.
- Nubulin: another large (nebulous) protein that associates with actin, helping to keep it organized.
Describe the morphological differences between skeletal, cardiac, and smooth muscle
- Skeletal muscle
- multinucleated
- striated
- cardiac muscle
- 1-2 nuclei
- striated
- intercalated discs connect adjacent cells
- Smooth muscle
- mononucleated
- non-striated
Describe the etiology, cellular consequences, and phenotype of hypertrophic cardiomyopathy
etiology:
-mutations in troponin or myosin heavy chain
Cellular consequences:
- cardiomyocyte + cardiac hypertrophy
- myocyte disarray
- interstitial and replacement fibrosis
- dysplastic intramyocardial arterioles
Phenotype:
- cardiac murmur
- cardiac pump failure (dyspnea, angina)
- arrhythmia
- sports/family screening
Describe the etiology, clinical features, and treatment of malignant hyperthermia
etiology:
- mutation of RyR1
- exposure to anesthetics (halothane and succinylcholine) causes the disorder
Clinical features:
- muscle rigidity (masseter tone)
- increased CO2 production
- Rhabodomyolysis
- hyperthermia
Tx:
-Dantrolene 2.5mg/kg
Describe the etiology and clinical features of Duchenne Muscular Dystrophy
Etiology:
- X-linked recessive
- many different genetic changes in dystrophin gene responsible for disorder
Clinical Features:
- tow-walking
- Gower’s sign
- calf pseudohypertrophy
- high creatine kinase
- cardiomyopathy 100% by 18yo
