PATCH-CLAMP ANALYSIS OF THE PROPERTIES OF ACETYLCHOLINE-RECEPTOR CHANNELS AT THE NORMAL HUMAN END-PLATE

Normative data were obtained on the kinetic properties of the acetylch oline receptor (AChR) channel at the human motor endplate by patch-cla mp analysis. Single channel currents were recorded from 34 endplates o f 8 nonweak subjects in the presence of 1 mu m acetylcholine (ACh) at 22 +/- 0.5 degrees C. The vast majority of channels opened to a conduc tance of about 60 pS. The dwell-time distributions of these channels w ere well described as the sum of two exponential functions. The mean d uration of the dominant longer component was 1.9 ms for the open inter vals and 3.04 ms for the bursts. At three endplates, a small proportio n of the channels had lower conductance and longer open time, resembli ng immature AChR channels. At 28 endplates it was also possible to obt ain an estimate of the rate constant for channel closure (alpha) and a pproximate estimates for the rate constants of channel opening (beta) and ACh dissociation (k(-2)). Estimates of k(-2) varied by 15% with me thods of estimation. This is attributed to errors inherent in estimati ng the duration of the briefest channel events. The normative data wil l be useful for evaluating pathologic alterations in the kinetic prope rties of the AChR channel found in some congenital myasthenic syndrome s. (C) 1994 John Wiley & Sons, Inc.