Physiology and Pharmocology of Skeletal Neuromuscular Junction Flashcards
(42 cards)
describe the cells which innervate skeletal muscle
myelinated axons of motor neurones divide into unmyelinated branches near the muscle
these branches then further divide into fine branches which end in a terminal bouton which form a chemical synapse at NMJ of a single muscle cell
each unmyelinated branch supplies one muscle cell
how is an action potential transferred to a muscle cell?
AP arises in cell body and conducted along axon to the boutons which causes the release of ACh
where are the cell bodies of motor neurones found?
ventral horn of spinal cord or brain stem
where do presynaptic terminals(boutons) synapse with the muscle cells?
endplate region
name 4 key features of the NMJ
- terminal bouton and surrounding schwann cells
- synaptic vesicles
- synaptic cleft
- end plate region of muscle cell membrane (sarcolemma) thrown into junctional folds
what are active zones at the NMJ?
where vesicles containing ACh are released
at the surface of the axon terminal
where are nicotinic ACh receptors located?
at regions of the junctional folds of the end plate region
face the active zones
what are the 5 stages of synaptic transmission at NMJ?
1 = synthesis of ACh 2 = Storage of ACh in vesicles 3 = release of ACh at active zones 4 = nicotinic ACh receptor activation 5 = transmitter inactivation
how is ACh synthesised?
cholins transported into terminal via choline transporter (Na+ symport)
choline combines with acetyl coenzyme A (from mitochondria) in cytosol with help from choline acetyltransferase enzyme
how is ACh concentrated in vesicles?
vesicular ACh transporter
how is ACh released from vesicles?
arrival of the action potential at the terminal causes depolarization and opening of voltage gated Ca2+ channels allowing Ca2+ entry to the terminal
Ca2+ causes vesicles which are docked at active zones to fuse with presynaptic membrane (exocytosis)
ACh diffuses into the synaptic cleft to activate post synaptic nicotinic ACh receptors in endplate region
what are the pre and post synaptic terminals?
pre = bouton post = end plate
what are nicotininc ACh receptors made up of?
pentamer of glycoprotein subunits which surround a central cation selective pore
how does a nicotinic ACh receptor work?
pore contains a gate which is closed when ACh is absent and open when 2 ACh molecules bind to the outside
when gate open - Na+ enters, K+ leaves (equally permeable)
how is an end plate potential created?
although equally permeable to both Na+ and K+, the driving force for Na+ is greater than that for K+ at resting potential so Na+ influx exceeds K+ efflux causing a depolarization called the end plate potential
what is a quantum?
a specific amount of ACh which is contained and released from all vesicles
what is the electrical response to a quantum of neurotransmitter at the end plate?
miniature endplate potential (MEPP)
how do MEPPs cause an EPP?
many MEPPs due to many vesicles being released summates to an EPP
because the number of MEPPs can vary this means that EPP is a graded response
what does an EPP do?
depolarizes end plate region enough that a threshold is reached and an action potential is triggered (due to opening of voltage activated Na+ channels)
is an AP a graded response?
no
all or nothing
what causes an EPP?
activation of nicotinic ACh receptors in end plate
graded
what does a single action potential in a motor neuron cause in a muscle cell?
1 AP in motor neuron = 1 AP in muscle = single twitch
how can drugs cause muscle weakness/paralysis?
can reduce amplitude of EPP so AP is never triggered
why are voltage gated Na+ channels required along the muscle cell?
without them the electrical event at the end plate would decline as it spread along the muscle and wouldnt excite so contraction could not occur
Na+ channels allow the AP to propagate over whole muscle fibre
