3. Muscular System 2 Flashcards
What are the 4 categories of skeletal muscle fiber phenotypes?
Force of contraction
Speed of contraction
Endurance
Oxidative/glycolytic capacity
Why must training be sustained for skeletal muscle?
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
What is remodeling in skeletal muscle?
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
What is Ca2+ role as a signal pathway in myofiber remodeling?
Ca2+ is primarily used as a second messenger for gene expression in the myofiber remodeling
What is the histone deacetylases (HDAC) and myocyte enhancer factor-2 (MEF2) interaction signalling pathway?
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
What is myocyte enhancer factor-2 (MEF2)?
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
What is the Calcineurin/nuclear factor of activated T cells (NFAT) signalling pathway?
Where is NFAT activity more commonly found?
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
What is Calcineurin?
Howbis it activated?
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
What is the peroxisome
-proliferator-activated receptor gamma coactivator-1 (PGC-1) signalling pathway?
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
What is peroxisome proliferator-activated receptor (PPAR)?
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
What is the AMP-activated protein kinase (AMPK) signalling pathway?
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
What is the Phosphatidylinositide 3-kinases (PI3K)/Akt (protein kinase B (PKB))/mammalian target of rapamycin (mTOR) signalling pathway?
(PI3K/Akt/mTOR)
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)
What does phosphorylated Akt inhibit?
Inhibits forkhead box (FOXO) nuclear entry thereby preventing protein degradation (FOXO is a transcription factor that regulates gene expression)
How is type 2 diabetes developed?
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
How does obesity decline contractile function if skeletal muscle?
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
What are muscle cramps?
How do you speed up relief?
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
What is creative kinase?
It’s 3 types?
What happened if it’s elevated?
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
What could be triggering mechanisms for cramping?
Exercise associates muscle cramps Fatigue Sweat loss Dehydration Electrolyte disturbances pH disturbances Thermal strain
What evidence suggests muscle cramping isn’t due to muscle?
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
What are pregnancy cramping?
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
What two endocrine diseases are associated with cramps?
Thyroid disease and hypoadrenalism
Cool extremities is one of the signs in hypothyroid patients (cool temperatures triggers cramp)
Hypoadrenalism could induce electrolytes imbalance it
Why are liver disease and cirrhosis associated with increased cramps?
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)
What is the threshold of a cramp?
The minimum frequency of electrical stimulation to induce a cramp
If stimulation impulse has low frequency, never have cramp
What are cramps abolished by?
Nerve block- blocking them nerve with neuroblocker (stimulating neuron requires a lot higher frequency)
What happens when a normal subject induced cramps by forceful contraction of an already shortened muscle?
Synchronous activation of different motor units occurs, suggesting a proximal (presumably central) trigger
How does cramp relieving by stretching work?
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
What are muscle spindles?
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
How do muscle spindles work in absence of gamma motor neurons?
Alpha activation
- Alpha motor neuron fires
- Muscle contracts
- Less stretch on center of intrafusal fibers
- Firing rate of spindle sensory neuron decreases
Slide 24 sept 17
