Effect of Limited Interval Resolution on Single Channel Measurements with Application to Ca Channels

Methods were developed by which measurements of single channel currents, multichannel currents or noise, and whole cell currents could be compared. The methods were applied to a particular set of voltage-dependent membrane channels, the calcium channels. parameters for a variety of identifiable models were estimated by obtaining the best fit to sets of whole cell current data. The parameter estimates were significantly "faster" than those obtained from histograms of measured single channel waiting, closed, and open time intervals (or WCO histograms). The whole cell current parameter estimates were used in Monte-Carlo simulations of single channels, and the effects of the low-pass filtering required to obtain reasonable experimental signal-to-noise ratios were evaluated. Errors that were introduced included the absence of brief open and closed times as well as falsely prolonged open and closed times. An analytical method was developed for computing the effects of these errors on the WCO histograms; following this computation, there was reasonable agreement between the whole cell and single channel measurements. The single channel simulations also allowed us to evaluate the effects of noise and finite record lengths. An unexpected finding was that a bimodal amplitude distributed could be produced by fltering simulated channels having only a single amplitude. This suggests that the occurrence of such a distribution may not necessarily be proof of the existence of two channel types.