#Mr X is a 25-year-old businessman . Over the last 6 months, he experienced "strange" symptoms. He had severe eyestrain when he read for longer than 15 minutes. He became tired when he chewed food, brushed teeth, he had extreme fatigue on the work. He does not like people not doing work on time but he himself is unable to do works at time due to fatigue. Serum was sent for Anti-AChR ab(antibody).
DISCUSSION:
Neuromuscular transmission is the process whereby an action potential in a motor neuron produces an action potential in the muscle fibers that it innervates. The steps in neuromuscular transmission, are as follows:
(1) An action potential is propagated down the motor neuron until the presynaptic terminal is depolarized.
(2) Depolarization of the presynaptic terminal causes voltage-gated Ca2+ channels to open, and Ca 2+ flows into the nerve terminal.
(3) Uptake of Ca2+ into the nerve terminal causes exocytosis of stored acetylcholine (ACh) into the synaptic cleft.
(4) ACh diffuses across the synaptic cleft to the muscle end plate, where it binds to nicotinic ACh receptors (AChR).
(5) The nicotinic AChR is also an ion channel for Na+ and K+, WhenACh binds to the receptor, the channel opens.
(6) Opening of the channel causes both Na+ and K+ to flow down their respective electrochemical gradients, As a result, depolarization occurs.
(7) This depolarization, called the end plate potential, spreads to neighboring regions of the muscle fiber.
(8) Finally, the muscle fibers are depolarized to threshold and fire action potentials, Through this elaborate sequence of events, an action potential in the motor neuron causes an action potential in the muscle fibers that it innervates.
In myasthenia gravis, abnormal antibodies to AChR (AChR-ab) are produced, circulate in the blood, and bind to nicotinic receptors on the muscle end plates. When antibodies are bound to AChR, the receptors are not available to be activated by ACh that is released physiologically from motor neurons. Thus, while normal action potentials occur in the motor neurons and ACh is released normally, the ACh cannot cause depolarization of muscle end plates. Without depolarization of muscle end plates, there can be no action potentials or contraction in the muscle.
After ACh binds to and activates AChR on the muscle end plate, it is degraded by acetylcholinesterase, an enzyme that is also present on the muscle end plate. This degradative step, whose byproducts are choline and acetate, terminates the action of ACh on muscle.
Pyridostigmine is an acetylcholinesterase inhibitor that binds to acetylcholinesterase and thereby prevents binding and degradation of ACh at the muscle end plate. In the treatment of myasthenia gravis, pyridostigmine prevents degradation ofACh, increases its synaptic concentration, and prolongs its action. The longer the muscle end plate is exposed to high concentrations of ACh, the greater the likelihood that action potentials and contraction in the muscle will occur.
He was given pyridostigmine.Mr X immediately felt better while taking the drug; his strength returned to almost normal.
