Excitation Contraction Coupling (ECC) Flashcards
what is myasthenia gravis caused by?
autoimmune response to ACh receptors (neuromuscular junction disease) so cannot initiate AP in muscle
-ptosis, weak smile, diploplia, speech slur symptoms: improve with edrophonium chloride (cholinesterase inhibitor to increase ACh at neuromuscular junction)
what is ALS amyotrophic lateral sclerosis a disease of?
motor neuron death in spinal cord
- loss of neuronal AP (reduced excitation)
- weakness, spasticity, muscle atrophy
what are demyelinating diseases caused by?
peripheral nerve disease b/c autoimmune VS myelin
- impaired neuronal AP propagation (reduced excitation)
- ascending paralysis, weakness
what is muscular dystrophy a disease of?
muscle disease (reduced attachment of muscle to ensheathing membrane)
- inefficient myofiber contraction, myofiber death (reduced contraction)
- muscle weakness and atrophy
what is malignant hyperthermia a disease of?
sarcomere disease (mutation of ryanodine receptor Ryr1 causing excessive Ca++ release into muscle)
- triggered by inhaled anesthetics
- excessive and prolonged myofiber contraction
- blood CO2 buildup, hyperthermia, circulatory collapse
can skeletal muscle contract in the absence of extraccellular Ca++?
yes, b/c Na+ dependent AP triggered by ACh release at neuromuscular junction triggers release of Ca++ from SR inside muscle cell/fiber
dihydropyridine (DHP) receptor
L-type Ca++ channel on T-tubule membrane, attached to ryanidine receptors of terminal cisternae
-changes structure with depolarization, to open ryanodine receptor channel gate
ryanodine receptor
Ca++ release channel attached to terminal cisternae
- opened by DHP receptor during depolarization
- causes Ca++ release into sarcoplasm, triggering sarcomere contraction
ryanodine and nanomolar and micromolar concentrations
[nanomolar] - binds to and opens ryanodine receptors
[micromolar] - closes ryanodine receptors
calcium induced calcium release (positive feedback)
SR releases Ca++ store rapidly
- ryanodine receptors open via DHP receptors and presence of cytoplasmmic Ca++
- this means that small amount of Ca++ released into sarcoplasm triggers adjacent ryanodine receptors (away from triad) to open and release Ca++ in positive feedback motion
- thus, Ca++ release occurs rapidly along entire length of SR, not just triad
what induces skeletal muscle relaxation?
when Ca++ is removed from sarcoplasm by Ca++ exchangers and pumps
mechanisms of Ca++ removal from sarcoplasm (3 types)
SERCA - uses ATP hydrolysis to pump Ca++ back into SR to be bound
PMCA - plasma membrane Ca++ ATPase that pumps 1 Ca++ out of the cell per 1 ATP
NCX - Na+ Ca++ exchanger that lets 3 Na+ into cell per 1 Ca++ out of cell
unfused tetanus
repetitive stimulation (summation) APs oscillate (hit AP during refractory period, but not soon enough to fuse)
what is the strength of contraction of skeletal muscle graded by? (3 things)
- rate ccoding, or frequency of stimulation
- recruitment of additional motor units
- size of motor units stimulated
fused tetanus
repetitive stimulation (summation) APs don’t oscillate (hit AP during refractory period soon enough to fuse)
treppe
steady increase in tension in successive twitches
- not summation, b/c tension returns to zero before next twitch
- occurs b/c Ca++ released from previous twitches excceeds Ca++ reuptake, causing increase in Ca++ concentration, thus increasing X-bridges that form
- also b/c frequent stimulation “warms up” muscle to increase enzymatic rate
what does Ca++ bind to within SR?
calreticulin and calsequestrin
what is a motor unit made of?
one motor neuron and multiple myofibers
-a single neuron will innervate multiple muscle fibers, but a single skeletal muscle fiber is innervated by only one neuron
small VS large motor units
small: single neuron and as few as 3 muscle fibers (extraoccular), in slow twitch
large: single neuron and 2000+ muscle fibers, in fast twitch
when motor unit activated, all innervated muscle fibers simultaneously stimulated
what is the order of small/large motor unit recruitment
Size principle - smaller motor units recruited first, then larger ones as more force is required
-fine control possible if recruit only few muscle fibers
how long does the energy supplied by ATP last?
1-2 seconds
how does phosphocreatine make ATP, and how long does its energy last?
PCr + ADP –> Cr + ATP
lasts 5-8 seconds
how does fermentation of glucose make ATP, and how long does its energy last?
glucose –> 2 lactic acid + 2 ATP
lasts 60 seconds (limited by lactic acid formation, not glucose amount)
how does oxidative metabolism of glucose make ATP, and how long does its energy last?
glucose + 6 O2 –> 6 CO2 + 6 H2O + 30 ATP
lasts 2-4 hours
how does oxidative metabolism of fats/CHO/PRO make ATP, and how long does its energy last?
FA + O2 –> CO2 + H2O + ATP
AA + O2 –> CO2 + H2O + urea + ATP
lasts many hours
muscle pain (burn)
due to lactic acid buildup when heavy muscle activity and low O2 cause muscle to reoly on fermentation to make ATP
- lactic acid accumulates in muscle fiber (burning)
- in heart = angina
what is angina?
buildup of lactic acid in cardiac muscle, b/c it is undergoing fermentation due to heavy activity and low O2
delayed onset muscle soreness
not correlated with lactic acid levels
- occurs in days following intense muscle use
- associated with muscle damage, maybe inflammatory response
muscle fatigue
decline in muscle tension due to muscle use, gradual depletion of SR Ca++ stores, and buildup of lactic acid and inorganic phosphates
- less maximal tension
- decreased shortening velocity (Vmax)
- slower rate of relaxation
- not due to low ATP
- may be adaptation to prevent rigor from low ATP level
what does low ATP favor?
stable actin myosin complexes, high Ca++ levels in sarcoplasm, thus rigor
high frequency fatigue
accompanies high intensity, short duration exercise
- due to failure in conduction of AP in T-tubule
- rapid recovery
low frequency fatigue
caused by low intensity, long duration exercises
- due to buildup of lactic acid and phosphates, which may change conformation of muscle PRO
- recovery is slow
