Patch-clamp analysis of the properties of acetylcholine receptor channels at the normal human endplate.

Normative data were obtained on the kinetic properties of the acetylcholine receptor (AChR) channel at the human motor endplate by patch-clamp analysis. Single channel currents were recorded from 34 endplates of 8 nonweak subjects in the presence of 1 micron acetylcholine (ACh) at 22 +/- 0.5 degrees C. The vast majority of channels opened to a conductance of about 60 pS. The dwell-time distributions of these channels were well described as the sum of two exponential functions. The mean duration of the dominant longer component was 1.9 ms for the open intervals and 3.04 ms for the bursts. At three endplates, a small proportion of the channels had lower conductance and longer open time, resembling immature AChR channels. At 28 endplates it was also possible to obtain an estimate of the rate constant for channel closure (alpha) and approximate estimates for the rate constants of channel opening (beta) and ACh dissociation (k-2). Estimates of k-2 varied by 15% with methods of estimation. This is attributed to errors inherent in estimating the duration of the briefest channel events. The normative data will be useful for evaluating pathologic alterations in the kinetic properties of the AChR channel found in some congenital myasthenic syndromes.