What is the safety factor in the pathogenesis of myasthenia gravis (MG)?

Updated: Aug 27, 2018
  • Author: Abbas Jowkar, MD; Chief Editor: Nicholas Lorenzo, MD, MHA, CPE  more...
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Answer

The amplitude of the EPP tends to be >60 mV above the muscle fiber resting membrane potential of -80 mV.  So only 15mV is needed to reach the threshold for action potential of -65 mV. The extra 45 mV is referred as the Safety Factor. So, even if the EPP were to get smaller (e.g., 40 mV) due to repetitive contraction resulting in fatigue, the EPP would still be high to reach threshold and maintain the one-to-one relationship between the action potential of the motor axon and generation of an action potential in the muscle cell. However, if the safety factor is greatly decreased as it may occur in MG, neuromuscular transmission may become blocked.

In MG, the safety factor is reduced (i.e., baseline EPP is reduced but still above threshold). Slow RNS (3 Hz) will cause depletion of ACh quanta and may drop the EPP below threshold, resulting in the absence of a muscle fiber action potential (a phenomenon referred to as presynaptic rundown). Consequently, EPP is reduced as there are fewer AChRs for ACh molecules to bind.


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