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

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Abstract
The amplitudes and time courses of miniature end-plate currents (mepcs) were compared at normal and myasthenic (MG) human end-plates studied under voltage clamp. The mepc amplitude at MG end-plates is reduced to about 1/3 normal; mean mepc (normal) = 2.6 .+-. 0.2 nA, mean mepc (MG) = 1.0 .+-. 0.1 nA. The decay time constant of mepcs (.tau.mepc) is very similar at normal and MG end-plates; .tau.mepc (normal) = 1.70 .+-. 0.1 ms .tau.mepc (MG) = 1.80 .+-. 0.13 ms (Vm [membrane potential] = -80 mV, T [temperature] = 23.degree. C). The equilibrium potential of the end-plate current (epc) at normal and myasthenic human end-plates is close to 0 mV. Decay time constants .tau.epc and .tau.mepc increase exponentially with membrane hyperpolarization. The voltage sensitivity of the time constants was similar at normal and MG end-plates. Both normal and myasthenic epc are greatly prolonged in the presence of neostigmine (10-6 g/ml). At the same time the voltage sensitivity of .tau.epc is slightly reduced. In response to steady ionophoretically applied ACh the mean membrane currents obtained at MG end-plates were smaller than the normal under similar conditions. 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-time (.tau.noise) was similar at the 2 sites: .tau.noise (normal) = 1.54 .+-. 0.04 ms, .tau.noise (MG) = 1.63 .+-. 0.11 ms; .gamma.(normal) = 22.3 .+-. 1.57 pS, .gamma. (MG) = 20.25 .+-. 1.93 pS (Vm = -80 mV, T = 23.degree. C). The voltage sensitivity of the channel life time, measured from end-plate current noise, was similar at normal and MG endplates. 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. The size of the transmitter packets released from MG-terminals is probably at least as large as the packet of the ACh released from normal human nerve terminals.

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