Muscle and Bone B&B

Question 1

define the following parts of the sarcomere:
a. Z disks
b. I band
c. A band
d. H band
e. M line

Answer 1

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

Question 2

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

Answer 2

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

Question 3

what is the function of the dihydropyridine receptors vs ryanodine receptors?

Answer 3

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

Question 4

these transporters transfer Ca2+ from the cytosol back into the sarcoplasmic reticulum of skeletal muscle cells, enabling muscle relaxation - what are?

Answer 4

SERCA: sarco/endoplasmic reticulum Ca2+ - ATPase

Question 5

what occurs in malignant hyperthermia?

Answer 5

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]

Question 6

dantrolene

Answer 6

muscle relaxant - antagonist of ryanodine receptors (release Ca2+ from SR)

Question 7

slow twitch vs fast twitch muscle fibers

Answer 7

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

Question 8

what is different about the use of calcium in skeletal vs cardiac muscle contraction?

Answer 8

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”)

Question 9

lusitropy

Answer 9

= myocardial relaxation (opposite of contractibility)

accompanies increase in contractility so that faster contraction is met with faster relaxation

mediated by SERCA channels

Question 10

what is the regulatory protein of SERCA channels in cardiomyocytes, and how is this inhibition removed?

Answer 10

phospholamban: inhibits SERCA channel

phosphorylation via beta adrenergic stimulation of PKA removes inhibition —> SERCA takes up more calcium for relaxation

Question 11

how is smooth muscle contraction and tone regulated? (2)

Answer 11

1. de/phosphorylation of MLC (myosin light chain) - only phosphorylated MLC can interact with actin
2. calcium availability - binds calmodulin to activate MLCK (myosin light chain kinase)

Question 12

what is the clinical use of dihydropyridine drugs?

Answer 12

(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

Question 13

what are the respective effects of the following second messengers on smooth muscle contraction?
a. cAMP
b. cGMP
c. IP3 (inositol triphosphate)

Answer 13

a. cAMP —> inhibits MLCK —> relaxation
b. cGMP —> activates MLC phosphatase —> relaxation

c. IP3 (inositol triphosphate) —> induces Ca2+ release from SR —> contraction

Question 14

nitric oxide is synthesized by endothelial cells from ____ and activates ______ 2nd messenger pathway

Answer 14

L-arginine

NO activates guanylyl cyclase —> cGMP —> activation of MLC phosphatase —> relaxation

Question 15

nitroglycerine vs nitroprusside

Answer 15

nitroglycerine: converted to NO in smooth muscle cells, treats angina and heart failure

nitroprusside: NO donor (immediate/direct), treats hypertensive emergency

Question 16

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

Answer 16

a. alpha1: Gq
b. alpha2: Gi
c. beta1: Gs
d. beta2: Gs
e. M1: Gq
f. M2: Gi
g. M3: Gq

Question 17

what type of bone is the patella?

Answer 17

sesamoid - embedded in tendons

Question 18

what is the effect of the following on bone turnover?
a. RANK-L
b. osteoprotegerin
c. M-CSF (macrophage colony stimulating factor)

Answer 18

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

Question 19

endochondral ossification vs membranous ossification

Answer 19

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)

Question 20

what is the cause of achondroplasia?

Answer 20

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

Question 21

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?

Answer 21

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

Question 22

what occurs in mucopolysaccharidoses, such as Hunter’s and Hurler’s syndromes?

Answer 22

lysosomal storage diseases characterized by inability to metabolize heparin and dermatan sulfate (mucopolysaccharides) —> accumulation causes chondrocyte death

presents with short stature and malformed bones

Question 23

what is the clinical use of teriparatide?

Answer 23

low dose once daily bolus of parathyroid hormone —> increases bone mass (trabecular bone)

used to treat osteoporosis

Question 24

contrast the effects of continuous vs low dose bolus of parathyroid hormone?

Answer 24

continuous PTH administration —> bone resorption, increased serum Ca2+ (reduces cortical bone)

low dose bolus PTH administration —> increased bone formation (increases trabecular bone)