MSK - NMJ Flashcards
what innervates skeletal muscle?
fast conducting alpha motor neurons with myelinated axons and cell Bodies in the spinal cord or brain stem
where does the axon divide into unmyelinated branches?
near the muscle to innervate individual muscle fibres
what is the motor unit?
the neurone and the number of fibres it innervates
what is the end of the branches?
terminal bouton that synapses with the muscle membrane at NMJ
what does an action potential cause?
release of transmitter Ach
where exactly is the synapse?
endplate region of skeletal muscle fibre
what contains the Ach?
synaptic vesicles which cluster at active zones
where are the nicotinic Ach receptors?
junctional folds that face the active zones
where is Ach synthesised?
cytoplasm of bouton
where is Ach stored?
synaptic vesicles
how is Ach released from the vesicles into the clefts?
Ca2+ dependant release by exocytosis
what happens once Ach is released?
brief activation of nicotinic receptors by reversible binding
what terminated the binding of Ach?
acetylcholinesterase
what terminates the binding of Ach?
acetylcholinesterase
pre-synpatically, how is choline transported into the terminal?
choline transporter (symport with Na+)
what is combined to produce Ach and by which enzyme?
choline and acetyl coenzyme A
choline acetlytransferase
what concentrates Ach in the vesicles?
vesicular Ach transporter
what does arrival of the action potential at the terminal cause?
depolarisation
opening of voltage gated Ca2+ channels
Ca2+ entry to the terminal
what does Ca+ cause the docked vesicles to do?
undergo exocytosis
how many ACh molecules activate each nicotinic receptor?
2
what are nAChRs?
pentamers of glycoprotein subunits surrounding a central cation selective pore
when does the pore/gate open?
when ACh binds
what is the channel equally permeable to and not permeable to?
Na+ and K+
anions
what happens when the gate is open?
Na+ enters and K+ exits simultaneously
how is a depolarising end plate potential generated?
influx of Na+ is greater (driving force at resting potential)
simultaneous opening of many nAChrs
what does each vesicle of Ach contain?
a quantum of neurotransmitter
what is a miniature end plate potential?
the electrical response to one quantum of transmitter
what is the graded electronic response?
when many MEPPs summate to produce an end plate potential
what is the condition for the end plate potential to cause contraction?
all or none reaction
it must exceed threshold to trigger contraction but this always occurs normally
what causes the contraction once the action potential is released?
release of Ca2+ from intracellular stores
how does the AP enter the muscle fibre?
transverse T tubules
what are transverse T tubules?
invaginations of cell membrane that dip into muscle cell
what do APs arriving at T tubules trigger?
release of Ca2+ from the SR
how does Ca2+ release cause the contraction?
by interacting with troponin assoc with myofibrils
what causes rapid termination of transmission?
hydrolysis of ACh by acetylcholinesterase
where do the end products choline and acetate go?
choline is taken up by the choline transporter
acetate diffuses from the synaptic cleft
how is the termination so rapid?
extremely efficient
some Ach molecules are hydrolysed before the transmitter has even bound to nicotinic receptors
which drugs reversibly block the action of AChE?
anti-cholinesterase
what is neuromyotonia?
disorders of muscle function including cramps, stiffness, slow relaxation and twitches
what causes acquired neuromyotonia?
AI
antibodies against K+ channels disrupt function
what do the antibodies in neuromyotonia cause?
hyper-excitability and repetitive firing
prolonged epp and repetitive AP discharge
what are used to treat neuromytonias?
anticonvulsants which block Na+ channels
main symptom of Lambert eaton myasthenic syndrome?
muscle weakness in limbs
what is assoc with LEMS?
small cell carcinoma of lung
origin of LEMS?
AI
antibodies against Ca+ channels
what are used to treat LEMS?
anticholinesterases to increase duration of ACh in cleft
potassium blockers to increase release of ACh
main symptoms of MG?
progressively increasing muscle weakness during period of activity
eye and eyelid weakness
origin of MG?
antibodies against ACh receptors
treatment of MG?
anticholinestrases and immunosuppressants
what is botulin toxin?
endotoxin that acts at motor neurone terminals to irreversibly inhibit ACh release
high death rate
what can a low dose of botulin toxin treat?
overactive muscles (dystopias) extra ocular muscles for squints or eyelids smoothing out wrinkles
what are curate like compounds?
interfere with the postsynaptic action of ACh by acting as competitive antagonists of the nicotinic receptors
what do curate like compounds cause?
reduction of amplitude of the epp to below the threshold for AP generation
what are curate like compounds used for?
induce reversible muscle paralysis in certain surgeries
