ENDPLATE CURRENTS AND ACETYLCHOLINE NOISE AT NORMAL AND MYASTHENIC HUMAN ENDPLATES

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. © 1979 The Physiological Society