Muscle and Bone B&B Flashcards
define the following parts of the sarcomere:
a. Z disks
b. I band
c. A band
d. H band
e. M line
a. Z disks: end of sarcomeres, contains vimentin/desmin and titin (tethers myosin)
b. I band: actin, near Z disks
c. A band: actin and myosin overlap between I bands, no change with contraction
d. H band: myosin
e. M line: central proteins for alignment/stability
fill in the blanks regarding muscle contraction:
1. initiated with calcium
2. ____ blocks binding groove for myosin
3. Ca2+ binds _______, triggering conformational change in ______
4. myosin binds actin and ATP is hydrolyzed
5. power stroke
fill in the blanks regarding muscle contraction:
1. initiated with calcium
2. tropomyosin blocks binding groove for myosin
3. Ca2+ binds troponin triggering conformational change in tropomyosin
4. myosin binds actin and ATP is hydrolyzed
5. power stroke
what is the function of the dihydropyridine receptors vs ryanodine receptors?
dihydropyridine receptors: between T-tubule (invagination) and sarcoplasmic reticulum, contain L-type Ca2+ channels —> conformational change with depolarization, which opens ryanodine receptors
ryanodine receptors: embedded in sarcoplasmic reticulum, releases Ca2+ upon activation to initiate contraction
these transporters transfer Ca2+ from the cytosol back into the sarcoplasmic reticulum of skeletal muscle cells, enabling muscle relaxation - what are?
SERCA: sarco/endoplasmic reticulum Ca2+ - ATPase
what occurs in malignant hyperthermia?
dangerous reaction to anesthetics in some patients (halothane, succinylcholine) —> fever, muscle rigidity after surgery
due to abnormal ryanodine receptors which release too much calcium —> consumption of ATP by SERCA for Ca2+ reuptake —> heat and tissue damage —> high creatine kinase and hyperkalemia
[treat with dantrolene - antagonist of ryanodine receptors]
dantrolene
muscle relaxant - antagonist of ryanodine receptors (release Ca2+ from SR)
slow twitch vs fast twitch muscle fibers
slow twitch (red): have extra myoglobin which resists fatigue + more mitochondria (efficient fatty acid metabolism)
fast twitch (white): primarily metabolize glucose and glycogen for efficient glycolysis
what is different about the use of calcium in skeletal vs cardiac muscle contraction?
skeletal - Ca2+ primarily from sarcoplasmic reticulum (dihydropyridine —> ryanodine receptors)
cardiac - Ca2+ influx from L-type channels triggers SR calcium release via ryanodine receptors (“calcium-triggered calcium release”)
lusitropy
= myocardial relaxation (opposite of contractibility)
accompanies increase in contractility so that faster contraction is met with faster relaxation
mediated by SERCA channels
what is the regulatory protein of SERCA channels in cardiomyocytes, and how is this inhibition removed?
phospholamban: inhibits SERCA channel
phosphorylation via beta adrenergic stimulation of PKA removes inhibition —> SERCA takes up more calcium for relaxation
how is smooth muscle contraction and tone regulated? (2)
- de/phosphorylation of MLC (myosin light chain) - only phosphorylated MLC can interact with actin
- calcium availability - binds calmodulin to activate MLCK (myosin light chain kinase)
what is the clinical use of dihydropyridine drugs?
(amlodipine, felodipine, nicardipine)
block L-type Ca2+ channels
effective against smooth muscle cells for inducing relaxation (less Ca2+ available to bind calmodulin and activate MLCK) —> decrease blood pressure in HTN
what are the respective effects of the following second messengers on smooth muscle contraction?
a. cAMP
b. cGMP
c. IP3 (inositol triphosphate)
a. cAMP —> inhibits MLCK —> relaxation
b. cGMP —> activates MLC phosphatase —> relaxation
c. IP3 (inositol triphosphate) —> induces Ca2+ release from SR —> contraction
nitric oxide is synthesized by endothelial cells from ____ and activates ______ 2nd messenger pathway
L-arginine
NO activates guanylyl cyclase —> cGMP —> activation of MLC phosphatase —> relaxation
nitroglycerine vs nitroprusside
nitroglycerine: converted to NO in smooth muscle cells, treats angina and heart failure
nitroprusside: NO donor (immediate/direct), treats hypertensive emergency
through which class of G proteins do the following receptors work?
a. alpha1
b. alpha2
c. beta1
d. beta2
e. M1
f. M2
g. M3
a. alpha1: Gq
b. alpha2: Gi
c. beta1: Gs
d. beta2: Gs
e. M1: Gq
f. M2: Gi
g. M3: Gq
what type of bone is the patella?
sesamoid - embedded in tendons
what is the effect of the following on bone turnover?
a. RANK-L
b. osteoprotegerin
c. M-CSF (macrophage colony stimulating factor)
a. RANK-L: expressed by osteoblasts, stimulates osteoclasts
b. osteoprotegerin: expressed by osteoblasts, decoy receptor for RANK-L (inhibits osteoclasts)
c. M-CSF (macrophage colony stimulating factor): secreted by osteoblasts, stimulates osteoclasts
endochondral ossification vs membranous ossification
endochondral: long bones develop from hyaline cartilage (during embryogenesis), osteoblasts replace chondroblasts/cytes
membranous: bone matrix forms directly by osteoblasts - lay down woven bone and later remodels into lamellar bone, formation of most flat bones (skull, face)
what is the cause of achondroplasia?
GOF mutation in fibroblast growth factor receptor 3 (FGFR3) (80% spontaneous, 20% AD) —> dwarfism
defective endochondral ossification - growth factor activated and inhibits chondrocyte proliferation —> short arms/legs, normal torso/head
Pt meets with a geneticist to determine the cause of their dwarfism. They have short arms and legs, but normally sized torso and head. Genetic analysis reveals a spontaneous mutation that affects endochondral ossification. What is the diagnosis?
achondroplasia: GOF mutation in fibroblast growth factor receptor 3 (FGFR3) (80% spontaneous, 20% AD) —> dwarfism
defective endochondral ossification - growth factor activated and inhibits chondrocyte proliferation —> short arms/legs, normal torso/head
what occurs in mucopolysaccharidoses, such as Hunter’s and Hurler’s syndromes?
lysosomal storage diseases characterized by inability to metabolize heparin and dermatan sulfate (mucopolysaccharides) —> accumulation causes chondrocyte death
presents with short stature and malformed bones
what is the clinical use of teriparatide?
low dose once daily bolus of parathyroid hormone —> increases bone mass (trabecular bone)
used to treat osteoporosis
contrast the effects of continuous vs low dose bolus of parathyroid hormone?
continuous PTH administration —> bone resorption, increased serum Ca2+ (reduces cortical bone)
low dose bolus PTH administration —> increased bone formation (increases trabecular bone)
