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