Excitation Contraction Coupling Flashcards
what does the action potential depolarization cause at the terminal button?
voltage gated calcium channels open and the elevated levels cause vesicles of ACh to fuse with the membrane
where does ACh from the motor neuron bind and what does this cause?
binds to channels in the muscle membrane and depolarizes the motor endplate with influx of Na and a minute amount of K efflux
what is the consequence of depolarization at the motor endplate?
opens voltage gated sodium channels that form an action potential down the muscle cell
how is ACh cleared from the synaptic cleft??
acetylcholinesterase inactivates the released acetylcholine.
what is the pathology of Myasthenia Gravis? How can it be treated?
autoantibodies target nicotinic ACh receptors at the neuromuscular junction
edrophonium chlorie decreases inactivation of ACh and increases the availability at the synapse
what are the symptoms of Myasthenia Gravis?
muscle fatigability that gets worse later in the day. hallmark symptoms are diploplia (double vision), ptosis and weakness of the smile
where, in the excitation contraction pathway, can disease mechanisms inhibit?
at the motor neuron, (along the axon and in the cell body), at the sarcomere, at the neuromuscular junction and in the muscle.
what is an example of a motor neuron disease?
ALS (motor neuron death in spine)
what is an example of a demyelenating disease?
Guilain-Barre syndrome (autoimmune response against myelin)
what is an example of a neuromuscular junction disease?
Myasthenia gravis (autoimmune response against ACh receptor)
what is an example of a sarcomere disease?
malignant hyperthermia (mutation in Ryr1 causing excessive calcium release in muscle)
what is an example of a muscle disease?
muscular dystrophy (reduced attachment to muscle membrane)
how does depolarization cause calcium release in muscle?
the T tubule is depolarized and ryanodine receptors in the sarcoplasmic reticulum open calcium channels
how much does Ca concentration increase after an action potential in a muscle cell?
from 10^-7 to 10^-5
where is the internal store of calcium inside the muscle? what are the implications of this reserve?
the sarcoplasmic reticulum
the cell can contract without extracellular calcium
what causes relaxation of the muscle cell?
calcium is transported back into the SR by ATPase ion pump
what binds calcium in the SR?
calreticulin and calsequestrin
what is the skeletal muscle triad composed of?
one T tubule (invagination of the cellular membrane) and 2 sarcoplasmic reticulum cisternae
how are the cisternae attached to the T tubule in the muscle triad?
by direct coupling of L-type calcium channels in the T tubule membrane to ryanodine receptors embedded in the SR membrane
what molecular changes does depolarization of the T tubule membrane cause?
change in the structure of the dihydropyridine receptor (L type Ca receptor) that opens a Ca channel gate in the ryanodine receptor in the SR membrane
what is ryanodine? What is its effect at higher and lower concentrations?
plant alkaloid that binds to SR calcium release channels (ryanodine receptors)
at very small concentrations it opens the receptors
at higher concentrations it closes the receptors
what is calcium induced calcium release? what effect does this cause?
ryanodine receptor is stiumated to open by the presence of cytoplasmic calcium
this causes calcium release along the entire SR, not just at the triad
what is the major mechanism for calcium removal in the muscle cell?
SR Ca ATPase pumps Ca back into the SR which binds to calreticulin and calsequestrin
what two mechanisms of calcium removal from the sarcoplasm extrudes calcium into the ECF?
plasma membrane Calcium ATPase that pumps one Ca from the cell in exchange for one ATP.
Na Ca exchanger lets 3 sodium into cell to remove one calcium
what is the temporal relationship among the action potential, calcium transient and tension development in the fast twitch fiber?
less than 5 ms between the action potential and Ca release.
shorter delay between calcium release and tension buildup but tension builds slowly (varies for different types of fibers)
what is twitch duration directly related to in muscle cells?
calcium transient duration- becomes briefer in faster twitch fibers
what type of summation is seen in muscle twitches? what effect does it have on tension?
muscle twitches show temporal summation that builds the tension over time
what is tetanus? what is the difference between fused and unfused tetanus?
a maintained contraction in response to repetitive stimulation
unfused tetanus is when the stimuli are far enough apart to cause the tension to oscillate and fused tetanus is caused when there is no time between oscillations for the tension to decrease
what is the strength of contraction of skeletal muscle graded by?
rate coding (frequency of stimulation) and recruitment of additional motor units
what is treppe? is it related to summation
the steady increase in tension in successive muscle twitches. unrelated to summation because each twitch relaxes back to zero before the next twitch
what is a presumed cause for treppe?
Ca reuptake results in an increase in Ca concentration (increased crossbridge formation)
what is a motor unit? how many motor neuron is each muscle cell innervated by?
one motor neuron and all myofibers innervated by it
only one
how many muscle fibers are controlled by a single large motor unit? in the smallest motor unit?
2000 fibers vs 3
what type of muscle fibers are in small and large motor units?
fast twitch fibers usually comprise large motor units and slow twitch muscle usually makes up small motor units.
are large motor units typically recruited automatically? in what situation are only small motor units required?
no, thy are recruited after small motor units need more force.
small motor units only when force requirement is low and control demands are high
what types of fibers are slow twitch and what are their properties?
type 1 fibers. they are fatigue resistant, myoglobin rich, glycogen poor, use oxidative metabolism and have many mitochondria
what are the two types of fast twitch fibers and how do they differ?
Type 2a and 2b fibers. 2a are more like slow twitch fibers with more glycogen. 2b fibers are very fast twitch, fatigable, and glycolytic in their metabolism
what is the sequence of energy usage in muscle cells related to usage duration?
ATP, phosphocreatine, anaerobic glucose metabolism, oxidative metabolism of glucose and oxidative metabolism of other organic compounds
how long does intramuscular ATP last during contraction? phosphocreatine?
1-2 seconds
5-8 seconds
how long does the muscle use anaerobic metabolism and what causes it to cease?
a minute
limited by lactic acid formation, not glucose amount
how does phosphocreatine provide energy to the muscle cell?
by transferring a phosphate to ADP
what causes muscle pain (burn)? what is this called in the heart?
anaerobic glycolysis producing lactic acid
in heart, called angina
is lactic acid in muscle always bad?
no, it may have a role in regulating muscle excitability during extreme exertion
what causes delayed onset muscle soreness?
muscle damage and possibly inflammatory response
what is muscle fatigue and what causes it?
decline in tension as a result of previous activity
caused by buildup of lactic acid and phosphates (not due to low ATP)
what is the adaptive advantage of muscle fatigue?
to prevent rigor that would result from a low ATP level
what is high frequency and low frequency fatigue? what are the causes?
high- accompanies short duration high intensity exercise because of a failure of action potential.
low- low intensity long duration exercise. due to buildup of lactic acid and phosphate (slow recovery)
