chap 6- NMJ, excitation-contraction coupling (b1- SMS) Flashcards
in the NMJ, what is the effective stimulus for causing acetylcholine release from the vesicles?
entry of calcium ions
explain the process at the NMJ of how acetylcholine is released into the synaptic cleft
nerve impulse reaches NMJ →
voltage-gated calcium channels open →
Ca2+ diffuses from synaptic cleft into inside of nerve terminal →
Ca2+ ions activate Ca2+-calmodulin-dependent protein kinase →
phosphorylates synapsin proteins →
detach the ACh vesicles →
ACh vesicles go into the active zone→
dock at release sites where they fuse w/ neural membrane and the ACh inside is emptied through exocytosis
whole process of how ACh are released from terminals into the synaptic space- now they have to cross this cleft to get to the other side to acc generate the end plate potential
what are synapsin proteins at the NMJ? what happens when they’re phosphorylated?
keep acetylcholine vesicles attached to the presynaptic terminal’s cytoskeleton
when phosphorylated → allow ACh vesicles to detach from the cytoskeleton
what are dense bars in the NMJ? what is their role?
special protein structures that have voltage gated calcium channels on each side
they function as aligner to position the ACh vesicles near active zones where they will be released
in the images, they’re the purple circles in the presynaptic membrane
what is neuromuscular junction by definition? neuromuscular transmission?
NMJ: junction b/w terminal branch of the nerve fiber & muscle fiber
neuromuscular transmission: mechanism by which motor nerve impulses initiate muscle contraction
explain the following terms:
- motor end plate
- synaptic trough
- synaptic cleft
motor end plate: thickened muscular layer that directly interacts w/ the nerve at the NMJ
- muscle’s “receiver” for nerve signals
synaptic trough: shallow depression in the motor end plate where nerve terminal sits
- invaginated membrane
synaptic cleft: space b/w the nerve terminal (presynaptic membrane) & membrane of muscle fiber (post synaptic membrane)
where is acetylcholine synthesized & stored?
synthesized by mitochondria in axon terminals and stored in vesicles at presynaptic membrane
what are subneural clefts? what is their function?
subneural clefts: the numerous folds in the postsynaptic membrane, located beneath the nerve terminal
- contain the nicotinic acetylcholine receptors at their entrance/mouth area
function: increase surface area
what is acetylcholinesterase and why is it important?
enzyme that rapidly destroys acetylcholine
- splits it into inactive choline & acetate
- half of choline taken back to pre synapse by Na-choline co-transport & used to synthesize new ACh
importance: prevents continued muscle re-excitation
what is end plate potential? what are the steps to generate it?
ACh travels across synaptic cleft →
binds to nicotinic ACh-gated ion channels on motor end plate of muscle →
cause conformational change that opens Na+ channels allowing Na+ to rush into muscle cell →
Na+ bring in positive charge w/ it → potential change inside muscle fiber called end plate potential →
end plate potential causes depolarization in neighboring voltage gated Na+ channels →
even more Na+ inflow that causes development of action potential to then cause muscle contraction
basically the depolarization caused by influx of Na+ ions is the end plate potential
what are 2 reasons that when sodium ions flow through the acetylcholine channels more than any other ions? (NMJ)
- Only positive ions flow through & there are only 2 in large concentration (Na+ in ECF, K in ICF)
- The inside of muscle membrane has a very negative charge potential that strongly pulls the positively charged sodium inside
myasthenia gravis symptoms + treatment
myasthenia gravis: autoimmune disease where antibodies block/destroy own acetylcholine receptors
- end plate potentials that occur are too weak to open voltage gated sodium channels = no depolarization
symptoms: muscle weakness, fatigue, drooping eyelids, difficulty breathing, more fatigue with exercise
treatment: neostigmine
- or some other anticholesterase drug that allows larger than normal amounts of ACh to accumulate in the synaptic space
excitation contration coupling definition
series of events linking muscle excitation (presence of an action potential) to muscle contraction (cross bridge activity that causes the thin filaments to slide)
*answer to the question “how does an electrical signal make a muscle move?”
explain the entire process of excitation-contraction coupling in skeletal muscle (how the nerve impulse causes muscle contraction)
action potential arrives at NMJ & releases ACh → signal travels to t-tubules that sense change →
cause conformational change in dihydropyridine (DHP) receptors →
opens ryanodine (RyR) Ca2+ release channels →
allows Ca2+ to diffuse rapidly into sarcoplasm → initiates muscle contraction (by Ca2+ binding to troponin → causes tropomyosin to move & uncover myosin-binding sites on actin → myosin heads can attach to actin- sliding filament theory)
explain the process of repolarization in skeletal muscle (muscle relaxing) in excitation-contraction coupling
conformational change in DHP receptor closes Ca2+ release channels →
Ca2+ is transported from sarcoplasm back to sarcoplasmic reticulum by ATP-dependent calcium pump called SERCA (sarcoplasmic reticulum Ca2+ - ATPase)
what is the effect of athletic training on muscles?
- increased muscle mass & size of muscle fibers
- increased utilization & coordination of motor units
- increased strength of tendons, ligaments, & bones
- increase storage of fuel in muscles
- increased blood supply to muscles
changes that occur inside hypertrophied muscle fibers
- increase number of myofibrils
- increase in mitochondrial enzymes
- increase in components of phosphagen metabolic system
- increase in stored glycogen
- increase in stored triglyceride
the most effective way to increase muscle mass is _________
resistance training
what is a t-tubule structurally?
invagination of the sarcolemma
its where the cell membrane drips into a mass of muscle
A scientist applies a toxin that prevents the repolarization of the sarcolemma by inhibiting potassium channels. How will this affect excitation-contraction coupling?
Prolonged depolarization, leading to sustained contraction
potassium is causing depolarization (action potential) that the DHP receptors are sensing to keep the channels open !!
3 ways that drugs can affect NMJ & their examples
- Having ACh-like actions (bind w ACh receptors)
- ex. methacholine, carbachol, nicotine -
Block NMJ transmission (used in anesthesia as well)
- ex. curariform drugs like d-tubocurarine -
Inactivating acetylcholinesterase
- ex. neostigmine, physostigmine, diisopropyl flurophosphate
effect of curare & organophosphate on NMJ
curare: AcH receptor blocker
- is non-depolarizing (competitive) inhibitor - doesn’t allow depolarization of muscles
organophospahte: AchE inhibitor
- is depolarizing (non competitive) inhibitor - constantly contracting muscle = paralysis
