End-plate currents and acetylcholine noise at normal and myasthenic human end-plates.

1. The amplitudes and time courses of miniature end-plate currents (m.e.p.c.s) have been compared at normal and myasthenic (MG) human end-plates studied under voltage clamp. The m.e.p.c. amplitude at MG end-plates is reduced to about one third normal; mean m.e.p.c. (normal) = 2.6 +/- 0.2 nA, mean m.e.p.c. (MG) = 1.0 +/- 0.1 nA. The decay time constant of m.e.p.c.s (tau m.e.p.c.) is very similar at normal and MG end-plates; tau m.e.p.c. (normal) = 1.70 +/- 0.1 msec, tau m.e.p.c. (MG) = 1.80 +/- 0.13 msec (Vm = - 80 mV. T = 23 degrees C). 2. The equilibrium potential of the end-plate current (e.p.c.) at normal and myasthenic human end-plates is close to 0 mV. 3. Decay time constants tau e.p.c. and tau m.e.p.c. increase exponentially with membrane hyperpolarization. The voltage sensitivity of the time constants was similar at normal and MG end-plates. 4. Both normal and myasthenic e.p.c.s are greatly prolonged in the presence of neostigmine (10(-6) g/ml.). At the same time the voltage sensitivity of tau e.p.c. is slightly reduced. 5. In response to steady ionophoretically applied ACh the mean membrane currents obtained at MG end-plates were smaller than the normal under similar conditions. 6. Analysis of end-plate current noise obtained during the steady application of acetylcholine (ACh) to voltage clamped normal and MG human end-plates showed that the amplitude of the elementary current event (gamma) and the average channel life-fime (tau noise) was similar at the two sites: tau noise (normal) - 1.54 +/- 0.04 msec, tau noise (MG) = 1.60 +/- 0.11 msec; gamma(normal) - 22.3 +/- 1.57 PS, gamma (MG) = 20.25 +/- 1.93 pS (Vm = - 80 mV, T = 23 degrees C). The voltage sensitivity of the channel life time, measured from end-plate current noise, was similar at normal and MG end-plates. 7. At normal human end-plates a packet of transmitter opens about 1500 channels whereas at MG end-plates a packet opens only about 600 channels. It is calculated that the size of the transmitter packets released from MG-terminals is at least as large as the packet of the ACh released from normal human nerve terminals.