The safety margin

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Figure 1 shows a schematic diagram of the structure of the neuromuscular junction (DreyerJ9.82). Vesicles containing quanta of acetylcholine molecules are generated and stored in the presynaptic nerve terminal and and are released from active zones in the presynaptic membrane. The active zones are sited opposite the synaptic folds of the postsynaptic muscle membrane where the acetylcholine receptors are most densely concentrated. When the nerve terminal is at rest, quanta of acetylcholine molecules are occasionally liberated spontaneously from vesicles. Some acetylcholine molecules will be destroyed by the enzyme cholinesterase in the synaptic cleft, but some molecules attach to acetylcholine receptors and cause a small change in membrane potential called the miniature endplate potential. This change of about 0.8 mV is small compared with the resting membrane potential of -70 mV and is not sufficient to stimulate a muscle contraction. However, when a nerve impulse arrives at the nerve terminal, a large number of acetylcholine quanta are released. The change in membrane potential greatly exceeds a critical firing threshold and muscle contraction takes place. The safety factor for neuromuscular transmission is the margin by which the change in membrane potential exceeds the critical firing threshold. In myasthenia gravis both structural changes in the architecture of the neuromuscular junction and dynamic alterations in the turnover of acetylcholine receptors erode the safety margin and efficiency of neuromuscular transmission.

Fig. 1 Schematic diagram of the neuromuscular junction showing active zones on the presynaptic membrane and synaptic vesicles located opposite the junctional folds of the postsynaptic membrane. Acetylcholine receptors are located in high density at the crests of the junctional folds. (Adapted with permission from Dreyer

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