3. Muscular System 2

Question 1

What are the 4 categories of skeletal muscle fiber phenotypes?

Answer 1

Force of contraction
Speed of contraction
Endurance
Oxidative/glycolytic capacity

Question 2

Why must training be sustained for skeletal muscle?

Answer 2

Transforming skeletal muscle resulting from exercise training involved more efficient use of oxygen to general ATP with a higher endurance level

But upon cessation of exercise training, the myosin heavy chain (MyHC) isoform transitions and metabolic changes are reversible

Question 3

What is remodeling in skeletal muscle?

Answer 3

It is a physiological response to exercise training

Involves primarily the activation of intracellular signalling pathways, causing alteration in:
Muscle mass
Contractile properties
Metabolic states

Transform and remodel to adapt to environmental demands

Question 4

What is Ca2+ role as a signal pathway in myofiber remodeling?

Answer 4

Ca2+ is primarily used as a second messenger for gene expression in the myofiber remodeling

Question 5

What is the histone deacetylases (HDAC) and myocyte enhancer factor-2 (MEF2) interaction signalling pathway?

Answer 5

In response to increase in intensity of activities which increases cytosolic [Ca2+], HDAC kinases are activates and lead to phosphorylation of HDACs which create dock site for chaperone protein 14-3-3 to bind to HDAC
Chaperone protein binding changed HDAC so it leaves nucleus and activates MEF2

HDAC causes hostones to wrap DNA tightly

Slides 9-10 sept 12

Question 6

What is myocyte enhancer factor-2 (MEF2)?

Answer 6

Protein in family of transcription factors that control gene expression and is an important regulator of cellular differentiation

Mediated tissue remodelling in stress response

Enhancing MEF2 DNA binding promotes muscle specific transcription

Question 7

What is the Calcineurin/nuclear factor of activated T cells (NFAT) signalling pathway?
Where is NFAT activity more commonly found?

Answer 7

Calcineurin is activates then dephosphorylates nuclear factor of activates T cells (NFAT) which translocates NFAT from cytoplasms to nucleus where it works on transcription factors to activate specific sets of calcium dependent target genes
Slides 12-15 sept 12

NFAT activity is found higher in slow muscle than is fast muscle
Also require for maintenance of slow myosin heavy chain gene expression and is involved in repression of fast myosin heavy chain IIb

Question 8

What is Calcineurin?

Howbis it activated?

Answer 8

A calcium and calmodulin dependant phosphatase
Consists of a calmodulin-binding catalytic A subunit and a calcium binding regulatory B subunit

Activated by sustained low amplitude calcium waves whicb make calcium bind to calmodulin
Is a sensor of contractile activity by sensing calcium fluctuations

Question 9

What is the peroxisome

-proliferator-activated receptor gamma coactivator-1 (PGC-1) signalling pathway?

Answer 9

PGC-1 is a transcriptional coactivator that regulates the genes involving in energy metabolism

Considered the master regulator of mitochondrial gene expression

Activates mitochondrial biogenesis and oxidative metabolism

Enriched in type I myofibers

Slide 16-17 sept 12

Question 10

What is peroxisome proliferator-activated receptor (PPAR)?

Answer 10

Major transcriptional regulator of fat burning in adipose tissue
Activation of PPAR showed an increase specifically in type I fibers

Exercise induction of PCG-1 May activate PPAR and induce myofiber remodeling

Question 11

What is the AMP-activated protein kinase (AMPK) signalling pathway?

Answer 11

Activates in response
to increase in workload which causes ATP depletion

AMPK activates both the uptake and oxidation of glucose and fatty acid
Inhibits synthesis of fatty acids, cholesterol and triglycerides

Slide 18 sept 12

Question 12

What is the Phosphatidylinositide 3-kinases (PI3K)/Akt (protein kinase B (PKB))/mammalian target of rapamycin (mTOR) signalling pathway?

(PI3K/Akt/mTOR)

Answer 12

Activated during hypertrophy

Nice with overexpressing of Akt showed increase in muscle mass, because of increase in muscle fiber size

Insulin-like growth factor (IGF-1) activates PAkt/mTOR by first activating phosphatidylinositide 3-kinases (PI3K) which causes phosphorylation of Akt

Activation of mTOR by Akt promotes protein synthesis and increases muscle mass (hypertrophy)

Question 13

What does phosphorylated Akt inhibit?

Answer 13

Inhibits forkhead box (FOXO) nuclear entry thereby preventing protein degradation (FOXO is a transcription factor that regulates gene expression)

Question 14

How is type 2 diabetes developed?

Answer 14

Reduced insulin stimulating glucose disposal

Skeletal muscle accounts for majority if insulin stimulated glucose intake

Activation of insulin receptor leads to increase production of glucose transporter 4 (GLUT4) and translocates to plasma membrane to enhance glucose uptake

Slides 23-24 sept 12

Question 15

How does obesity decline contractile function if skeletal muscle?

Answer 15

Increase insulin secretion, inhibit DGK-δ, adiponectin activation, disrupt Ca2+ signalling
Leading to suppression in AMPK activity promoting fat deposition and a shift to fast muscle fibers

Question 16

What are muscle cramps?

How do you speed up relief?

Answer 16

Sudden onset of painful, involuntary squeezing or contraction of muscle
Often hard knot in muscle
Can come anytime (usually don’t do anything to trigger it)
Usually in one muscle or part of a muscle
Commonly lower limb muscles (calf foot thigh muscles)

Speed up relief (unlock cramp) by stretching the affected muscle or contraction of its antagonist muscle

Question 17

What is creative kinase?
It’s 3 types?
What happened if it’s elevated?

Answer 17

Creatine kinase comes in 3 isoforms:
MMCK- muscle
MBCK- heart
BBCK- brain (CNS)

If MM elevated, muscle damage, hypoxic or metabolic damage
If MB elevated, heart attack
If BB elevated, brain damage

Question 18

What could be triggering mechanisms for cramping?

Answer 18

Exercise associates muscle cramps
Fatigue
Sweat loss
Dehydration
Electrolyte disturbances
pH disturbances 
Thermal strain

Question 19

What evidence suggests muscle cramping isn’t due to muscle?

Answer 19

There are spontaneous discharges from the motor neuron inner sting the affected muscle

Need action potential for muscle cramp
Motor neuron must trigger muscle contraction
Muscle cannot generate action potential

Monitor muscle cramps on EMG (electromyogram) to reveal that there are involuntary repetitive high frequency firings of the motor neuron that innervated the cramping motor unit (comes from peripheral nerves)
Loss or damage of lower motor neurons are associated with cramps

Question 20

What are pregnancy cramping?

Answer 20

The third trimester of pregnancy is associated with leg cramps in up to 30% of women
Increase of body fluid to supply nutrients to fetus
Fluid retention stretches structure and neuromuscular junction

Question 21

What two endocrine diseases are associated with cramps?

Answer 21

Thyroid disease and hypoadrenalism

Cool extremities is one of the signs in hypothyroid patients (cool temperatures triggers cramp)

Hypoadrenalism could induce electrolytes imbalance it

Question 22

Why are liver disease and cirrhosis associated with increased cramps?

Answer 22

The decrease in intravascular volume

Albumin when I fused decreases the frequency of cramps in some cirrhotic patients
Albumin increases osmolarity gradient (enhances circulation, decrease frequency of the cramp)

Question 23

What is the threshold of a cramp?

Answer 23

The minimum frequency of electrical stimulation to induce a cramp

If stimulation impulse has low frequency, never have cramp

Question 24

What are cramps abolished by?

Answer 24

Nerve block- blocking them nerve with neuroblocker (stimulating neuron requires a lot higher frequency)

Question 25

What happens when a normal subject induced cramps by forceful contraction of an already shortened muscle?

Answer 25

Synchronous activation of different motor units occurs, suggesting a proximal (presumably central) trigger

Question 26

How does cramp relieving by stretching work?

Answer 26

Voluntary contraction of the antagonist muscle is mediated through central inhibition
Cramp will still go away without stretch just longer

There are involuntary repetitive high frequency firings if the motor neuron that innervates the cramping motor unit when stretching

Increase in frequency if afferent signals to spinal cord through the muscle spindles sensory neuron which increases frequency of efferent signals to the stretched (cramping) muscle through alpha motor neuron

Slide 25 sept 17

Question 27

What are muscle spindles?

Answer 27

Stretch receptors that can be found in the capsules if the extrafusal muscle fibers

Muscle spindles are tonically active and firing even when muscle is relaxed

Muscle spindles stretch so bone doesn’t change

Slides 19-23 sept 17

Question 28

How do muscle spindles work in absence of gamma motor neurons?

Answer 28

Alpha activation

1. Alpha motor neuron fires
2. Muscle contracts
3. Less stretch on center of intrafusal fibers
4. Firing rate of spindle sensory neuron decreases

Slide 24 sept 17