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Post-junctional Acetylcholine Receptors

The acetylcholine receptors are nicotinic and are either 1) Junctional/ mature or 2) Extra junctional/ immature. Along the neuromuscular junction, post-junctional receptors are only found in the area of the end plate, opposite that of the pre-junctional receptors. However, extra-junctional receptors are present throughout skeletal muscles. Normally, the development of these extra-junctional receptors is suppressed by neural activity. Prolonged inactivity, sepsis, denervation, or traumas (burn injury) to skeletal muscles are associated with a proliferation of extra-junctional receptors.

When a large number of extra-junctional receptors are present, there are clinical implications. These extra-junctional receptors allow depolarizing neuromuscular blockers (succinylcholine) to cause widespread depolarization and extensive potassium release. Part of the reason for this severe response is based on the fact that these extra-junctional receptors have a longer opening time of the ion channel compared to junctional receptors which leads to a larger efflux of potassium. This risk of hyperkalemia is believed to peak in 7-10 days following injury, however the exact timeframe of onset and duration varies.

Compared to depolarizing neuromuscular blockers, when a large number of extra-junctional receptors are present, resistance to NDMR develops. This can be related to increased susceptibility of the muscle membrane to depolarization by ACh, however the exact mechanism is still unclear.

Other References

  1. Jung KT, An TH. Updated review of resistance to neuromuscular blocking agents. Anesthesia Pain Med 2018; 13:122-127 Link