Skeletal and smooth muscle

Question 1

Individuals with prolonged immobilization experience atrophy of what type of muscle fibers?

Answer 1

Atrophy of type I fibers (slow twitch) and reduced diamter of type II fibers

At the same time capillary density in the immobilized muscles will decline

Question 2

What detects the length of stretch or shortening in muscle?

Answer 2

Muscle spindles detect length of stretch (or shortening) as well as the velocity of contraction

Question 3

Golgi tendon organs

Answer 3

Sense the force generated by a muscle gaugin the tension developed in muscle tension

Question 4

X-linked muscular dystrophy

Answer 4

Duchenne’s muscular dystrophy

Skeletal muscle is replaced by adipose tissue

X-linked recessive - affects boys>girls

LOF mutation - deletion of gene that codes for dystrophin (largest gene in the human genome - highest risk of error)

Dystrophin- cell membrane protein that allows for interaction of the muscle fiber with extracellular matrix.

Disease is progressive, from proximal skeletal muscle outward toward the distal muscles

Presents around 1 y/o - affects quadriceps first (difficulty walking)

Total paryalysis by second decade of life - death occurs as result of myocardial infiltration

Question 5

Gower’s sign

Answer 5

The unusual way in which a child w/ x-linked muscular dystrophy will use a series of hand pushes to rise from the ground - unable to rely on hip flexors or shoulder muscles

Question 6

Becker’s muscular dystrophy

Answer 6

Same disease as Duchenne’s except there’s a mutation of the dystrophin gene rather than a deletion

Because there is some protein as opposed to none - disease is often milder

Question 7

Myasthenia gravis

Answer 7

Autoimmune disorder caused by antibodies against postsynaptic nicotinic ACh receptors - binding of Ab’s competively inhibits ACh from binding

Decaying force of contraction on rapidly repeated contractions

Small muscles and muscles that are used a lot are affected most

Pt’s will c/o blurry bision, dysphagia, and difficulty writing

Pt’s with MG can sometimes have a hyperproliferation of mediastinal thymic tissue (thymom) - removal can reverse sxs of MG

Question 8

Myasthenia gravis vs. Lamber-Eaton syndrome

Diagram

Answer 8

Question 9

Lambert-Eaton Myasthenic Syndrome

Answer 9

More than 1/2 cases are associated w/ small cell lung cancer - Tx’ing the cancer helps resolve the sxs

Due to antibodies against voltage-gated calcium channels on presynaptic nerve terminals leading to a decrease in ateylcholine release

W/ successive presynaptic action potneitlas that temporally sum, ACh will be released and contraction will occur. Increasing frequency of contraction increases the strength of contraction - muscles not often used are first affected

Question 10

myotonias

Answer 10

Are conditions characterized by the impairment of muscle relaxation following voluntary contraction or electrical stimkulation.

One sign is the inability to loosen a handgrip after lifting a heavy object or after a handshake

Question 11

Myotonic dystrophy 1

Answer 11

Results from synthesis of a defective RNA that sequesters RNA binding proteins causing dysregulated RNA splicing. This leads to down regulation of a voltage-gated Cl channel (ClC1) involved in stabilizing muscle cell membrane potentials

Fx loss of this ClC1 leads to myotonia

Question 12

Congenital myotonia

Answer 12

Results from a defect in the CLCN1 gene - encodes for ClC1 protein

TN fainting goats - result from a mutation in CLCN1

Question 13

Malignant hyperthermia (MH)

Answer 13

Hereditary disorder of skeletal muscle - hypermetabolic response to halogenated anesthetic gasses and/or depolarizing muscle relaxant succinylcholine

Mutation in the ryanodine receptor results in uncontrolled release of calcium from skeletal muscle SR leading to sustained muscle contraction.

Dantrolene inhibits the ryanodine receptor calcium release channel in skeletal muscle without affecting nueromuscular transmission and is effective for both prophylaxis and tx of active MH

Question 15

Myofilament composition

Answer 15

Myosin 2 and actin - make up the contractile unit (sarcomere)

Question 16

Myosin vs actin on ESM

Answer 16

Myosin - appear darker than actin on an electron micrograph

Areas of overlap between myosin and actin appear darkest of all

Question 17

Zones/bands of the sarcomere

Answer 17

Question 18

During contraction which lines of the sarcomere get closer together?

Answer 18

The Z lines get closer together

Question 19

During muscle contraction, what organelle propagates the action potential?

Answer 19

The T-tubule

Depolarization activates and opens the gate of T-tubule voltage-gated L-type calcium channels - do not allow for sufficient calcium movement to cause contraction (because they arent in the sarcoplasmic reticulum)

Question 20

T-tubule L-type Ca²⁺ channels open what other channels?

Answer 20

They physically open the sarcoplasmic-reticulum-ryanodine-Ca²⁺ channels - this calcium influx is sufficient to induce contraction

Question 21

Troponin I

`

Answer 21

Physically in the way covering the myosin-binding site on actin

Question 22

Troponin T (TnT)

Answer 22

Pushes tropomyosin aside

Question 23

Answer 23

There is optimal overlap between the actin and myosin filaments

Question 24

A single contraction of skeletal muscle is most likely to be terminated by?

Answer 24

Removal of sarcoplasmic Ca²⁺

Question 25

Why does rigor mortis set in?

Answer 25

Decreased ATP levels

Question 26

The diagram illustrates the isometric length-tension relationship in a representative intact skeletal muscle. Use the letters in the diagram to identify the contribution of non-contractile muscle elements to total tension.

Answer 26

C

Question 27

Tetanic contraction of a skeletal muscle fiber results from a cumulative increase in the intracellular of?

Answer 27

Ca²⁺

Question 28

Which of the following situations is most likely to increase the proportion of Type I fibers in skeletal muscle?

Answer 28

Aging

Question 29

Primary source of ATP in type 1 and type 2B fibers

Answer 29

Type I - oxidative phosphorylation Type 2 - glycolysis

Question 30

Myoglobin content in type 1 vs. type 2B fibers

Answer 30

Type 1 - high Type 2B - low

Question 31

Duchenne's muscular dystrophy we see a decrease in what fibers first?

Answer 31

Fast twitch, specifically type IIX

Question 32

What type of muscle fiber increases with type II diabetes?

Answer 32

The fast twitch muscle fibers increase with type II diabetes

Question 33

Mini end-plate potentials

Answer 33

Are single vesicles that are released and produce a small 0.4 mV voltage deflection These are calcium independent processes - why mini end-plate potentials are normal in Lambert-Eaton syndrome (impaired presynaptic volateg-senesitive Ca channels)

Question 34

What is the "sensor" for smooth muscle

Answer 34

Calmodulin

Question 35

What inhibits the contraction in smooth muscle

Answer 35

Phosphatase

Question 36

Multi-unit smooth muscle

Answer 36

Electrical isolation of smooth muscle cells allows for finer motor control ## Footnote Iris and ciliary body of eye Piloerector muscle Larger blood vessels Smaller airways

Question 37

Unitary (visceral) smooth muscle

Answer 37

Gap junctions permit coordinated contraction ## Footnote Gut Uterus Arterioles Bladder

Question 38

Action potential of smooth muscle | Comparison to other muscle

Answer 38

Question 39

Phasic vs. Tonic contraction of smooth muscle

Answer 39

Question 40

Calcium interacts with troponin on the _________ , in skeletal muscle

Answer 40

Calcium interacts with troponin on the **thin filaments** in skeletal muscle

Question 41

In smooth muscle, calcium binds to _______ , activates ______ ______ _____ ______ , which then activates (by phosphorylation) __________

Answer 41

In smooth muscle, calcium binds to **calmodulin**, activates a **myosin light chain kinase (MLCK)**, which then activates (by phosphorylation) **myosin light chains**.

Question 42

Calcium activates ______ in skeletal muscle, while it activates ______ in smooth muscle

Answer 42

Calcium activates **thin filaments** in skeletal muscle, while it activates **thick filaments** in smooth muscle.

Question 43

Excitation contraction coupling in smooth muscle | The calcium signal diagram

Answer 43

Question 44

Excitation contraction coupling in smooth muscle | List the different types

Answer 44

Electrical coupling - voltage gated Ca²⁺ channels open when the cell is depolarized - can be action potential or subthreshold depolarization Pharmaco- (mechanical) coupling: 1. Cell membrane ligand gated Ca²⁺ channels 2. Ligand generation of IP₃ which initiates Ca²⁺ release from SR Both mechanisms may operate at the same time (norepi and serotonin can activate both pathways in the same cell)

Question 45

Biochemical agents that stimulate contraction of smooth muscle

Answer 45

ACh NE Angiotensin II

Question 46

Smooth muscle that exhibits rhythmical contraction in the absence of external stimuli also necessarily exhibits which of the following? A. Intrinsic pacemaker wave activity B. Higher resting cytosolic Ca²⁺ concentration C. Hyperpolarized memebrane potential D. Action potentials with "plateaus"

Answer 46

Intrinsic pacemaker wave activity ## Footnote Generally seen in GI smooth muscle

Question 47

The sensitivity of the smooth muscle contractile apparatus to calcium can be altered by calcium-independent mechanisms. An increase in calcium sensitivity can be attributed to a decrease in the levels of which of the following substances?

Answer 47

Myosin light chain phosphatase (MLCP) activity

Question 48

The delayed onset and prolonged duration of smooth muscle contraction, as well as the greater sustained force generated by smooth muscle compared with skeletal muscle, are all consequences of which of the following?

Answer 48

Slower cycling rate of the smooth muscle myosin cross-bridges

Question 49

Which of the following best describes an attribute of visceral smooth muscle not shared by skeletal muscle?

Answer 49

Contractions in response to stretch

Question 50

Smooth muscle contractions are highly resistant to fatigue because:

Answer 50

Slow cross bridge cycling and dephosphorylation of myosin light chains in the latched state

Question 51

Unitary and multi unit smooth muscle differ in this characteristic or property.

Answer 51

Unitary smooth muscle cells are connected by gap junctions but multiunit smooth muscle are not

Question 52

Smooth muscle contraction is terminated by?

Answer 52

Dephosphorylation of myosin light chain

Question 53

Which of the following best describes an attribute of visceral smooth muscle not shared by skeletal muscle?

Answer 53

Contractions in response to stretch Stretching smooth muscles opens mechanically gated Ca²⁺ channels which induces contraction

Question 54

During pregnancy, why does the uterus behave as a unitary smooth muscle?

Answer 54

Estrogen promotes gap junction formation between smooth muscle cells

Question 55

Nitric oxide MOA | Diagram

Answer 55

Question 56

A drug that causes muscle tightness is likely inhibiting which of the following transporters? A. Voltage-gated sodium channels B. Sarcoplasmic ER ATPase (SERCA) C. Ryanodine receptor calcium channel D. Dihydropyridine receptor, L-type calcium channel E. Nicotonic acetylcholine receptor

Answer 56

B. Sarcoplasmic reticulum endoplasmic reticulum ATPase (SERCA)

Question 57

A defect in which of the following proteins produces malignant hyperthermia? A. AChR B. Mysoin light chains C. SERCA D. Ryanodine receptor calcium channel E. L-type (dihydropyrodine receptor) calcium channel

Answer 57

D. Ryanodine receptor calcium channel

Question 58

Ion flux through what channel is associated with the upstrok of action potentials and contraction in smooth muscle?

Answer 58

Voltage-gated calcium channels

Question 59

Ragged red fiber

Answer 59

Due to **defective oxidcative phosphorylation** Occurs in Pt's w/ myoclonic epilepsy w/ ragged red fiber (MERRF) due to point mutations in mitochondrial DNA that result in dysfunction of proteins in the ETC Has **variable expression** within families due to heteroplasmy (heterogeneity of mDNA within a cell - caused by selective distribution of mitchondria w/ mutated DNA) ## Footnote MERRF causes myoclonus, ataxia, weakness, and generalized epilepsy Muscle fivbers w/ red inclusions that disrupt the normal fiber contour

Question 60

An investigator is studying muscle contraction in tissue obtained from the thigh muscle of an experimental animal. After injection of radiolabeled ATP, the tissue is stimulated with electrical impulses. Radioassay of these muscle cells is most likely to show greatest activity in which of the following structures? ## Footnote AMBOSS

Answer 60

The outer segments of the **A band** are the sites where actin and myosin filaments overlap and form cross-bridges via the myosin heads, which bind and hydrolyze ATP. Following injection of radiolabeled ATP, radioassay is most likely to show the greatest activity in the A band of the sarcomere. ## Footnote AMBOSS