an action potential travels down a motor nerve and
reaches the nerve terminal, acetylcholine (ACh) molecules
are released from the presynaptic vesicles and adhere
to AChR at the peaks of postsynaptic folds. Channels
in the AChR open, allowing Na+ and other cations to
enter into the muscle fiber endplate and depolarize
it. The multiple depolarizations will sum up, and
if large enough, trigger an action potential, which
travels along the muscle fiber to produce contraction.
With every nerve impulse, the amount of ACh released
by the presynaptic motor neuron normally decreases
due to a temporal depletion of the presynaptic ACh
stores (presynaptic rundown).
Myasthenia Gravis (MG), there is a reduction in the
number of AChR available at the muscle endplate and
flattening of the postsynaptic folds. The fewer endplate
potentials produced by the yet normal amount of ACh
released might fail to be translated into an action
potential. The end result is an inefficient neuromuscular
transmission. This inefficient neuromuscular transmission
together with the normally present presynaptic rundown
phenomenon results in a decremental amount of nerve
fibers being activated by successive nerve fiber impulses.
This explains the fatigability in the involved patients.
decrease in number of the postsynaptic AChR is believed
to be due to an autoimmune process whereby anti-AChR
antibodies are produced and act to block the target
receptors, increase their turnover, and damage the
postsynaptic membrane in a complement-mediated manner.
Although the primary etiology remains speculative,
there is increasing evidence that the thymus might
play an important role.
studies showed prominent germinal centers. Epithelial
myoid cells normally present in the thymus do resemble
skeletal muscle cells and possess AChR on their surface
membrane. These cells may become antigenic and unleash
an autoimmune attack on the muscular endplate AChR
by molecular mimicry.
the disease afflicts first and predominantly the extraocular
muscles remains unanswered. It probably has to do
with the physiology and antigenicity of the muscles