On the release of transmitter at normal, myasthenia gravis and myasthenic syndrome affected human end‐plates.

1. Transmitter release has been studied at normal, myasthenia gravis (m.g.) and myasthenic syndrome (m.s.) affected human end‐plates. At normal and diseased end‐plates evoked transmitter release is Poisson for a mean quantal content, m less than ten. 2. The relation between log m and log [Ca]o, at normal and m.g. end‐plates is linear, with a slope of 3.3‐3.4. The value of m at m.g. end‐plates is about five times larger than normal, below Ca 0.7 mM (Mg, 2mM). This difference in m is reduced at higher Ca levels. 3. The slope of the relation between log m.e.p.p. frequency and log [K]o is similar at normal and m.g. end‐plates. Over its linear portion the relationship has a slope of approximately 6. 4. Fluctuations in the latency of evoked transmitter release were compared at normal and m.g. nerve terminals. At normal end‐plates the probability of release reaches a peak about 0.3‐0.4 msec after unitary e.p.p.s of the shortest latency and returns to zero about 1.0 msec after the peak. At m.g. end‐plates the distribution of latencies shows less uniformity. 5. At m.s. end‐plates m is approximately 5 in normal Ringer solution (2 mM‐Ca, 1 mM‐Mg). The relation between log m and log [Ca]o is linear, with a slope of 1.0‐1.5. The K dependence of m.e.p.p. frequency appears reduced at m.s. end‐plates. 6. Assuming a co‐operative mechanism for transmitter release at normal human motor nerve terminals, the dissociation constant for the Ca complex is about 1.6X10(‐3) M and the dissociation constant for the Mg complex is about 1.0X10(‐3) M. 7. It is concluded that the presynaptic changes, at m.g. end‐plates, are not the primary cause of the defect in nerve muscle transmission. At m.s. end‐plates the presynaptic changes are sufficient to account for failure in transmission. Possible mechanisms for the abnormalities in transmitter release are considered.