Neuromuscular Transmission Failure: Myasthenia Gravis and Lambert-Eaton

Myasthenia gravis is a perturbation of the force-frequency machinery (§2). Post-synaptic ACh-receptor block raises the per-pulse activation threshold, so during low-frequency repetitive stimulation transmitter run-down makes successive pulses fall short: force DECREMENTS pulse-to-pulse. At 3 Hz the model gives a 18.4% decrement versus 0.02% normal — above the 10% clinical RNS threshold, and monotone in lesion severity [V].

The same depression+facilitation NMJ that drives T1 is pushed past its safety factor: at 3 Hz the decrement rises from 0.02% (normal) to 18.4% (MG), crossing the cited >10% diagnostic line, and grows with the lesion (sweep below). Lambert-Eaton is the mirror: a presynaptic deficit with use-dependent facilitation gives a high-frequency INCREMENT (+46.7% at 50 Hz), the opposite sign. Direction + threshold [V]; clinical sign cited [L].

Decrement = transmission below its safety factor

Neuromuscular transmission normally has a large safety factor: each motor nerve impulse releases far more ACh than needed to fire the fibre, so T1's force-frequency curve is flat pulse-to-pulse at low rates. Myasthenia gravis blocks post-synaptic ACh receptors, cutting that safety margin. Now the physiological run-down of release during a 2–5 Hz train drops successive end-plate potentials below the firing threshold, and the muscle force decrements — the classic repetitive nerve-stimulation (RNS) sign. This is the SAME NMJ model used in T1 with the threshold raised; no new mechanism.

Above the cited diagnostic line, and dose-dependent

At 3 Hz the modelled decrement is 18.4% against 0.02% in the unblocked junction, clearing the cited >10% RNS threshold. Deepening the block (lower safety factor) monotonically deepens the decrement:

Lambert-Eaton: the opposite sign

Lambert-Eaton myasthenic syndrome is a PREsynaptic deficit: baseline release is low (a weak first response) but use-dependent facilitation builds up during high-frequency activity, so the response INCREMENTS. The model reproduces the reversal — an increment that grows with frequency:

MG decrements at low frequency; LEMS increments at high frequency. The kit reproduces both DIRECTIONS from one NMJ, which is the discriminant.

Seam and what is NOT claimed

The synaptic CAUSE (autoantibody against the ACh receptor or the presynaptic calcium channel) is owned by the neuro / immune volumes and only cited here; the in-class result is the muscle-side force change. The clinical threshold is cited [L]. One limit is recorded [O]: this depression-only NMJ does not model high-frequency post-activation potentiation, so the brief facilitation seen in MG at high rates is out of scope.