Parametric survival analysis for gating kinetics of single potassium channels

Abstract

The gating mechanism and the role of the S4 region in the activation of Shaker potassium channel was studied by statistical analysis on the wild type and mutant channels which have mutations in the S4 region. Single channel currents were recorded with the patch-clamp technique. The first latency time was analyzed with a parametric survival time regression model in which the generalized gamma distribution for the error term was assumed. Discrimination among Weibull, gamma, log-normal and exponential distributions was done with the likelihood ratio test. The three-parameter generalized gamma distribution was shown to be appropriate for the data set. The multiple regression function provides the statistical tests and the quantitative descriptions for the relationships between the mutations and the voltage dependence of the gating process. These results on statistical relations support the hypothesis that the S4 region plays an important role in sensing transmembrane voltage in the gating process, but the gating mechanism is not solely accounted for by the electrostatic interaction between the charged amino acids and the transmembrane voltage field. This work demonstrates that the survival analysis procedures can be useful tools for analyzing neurophysiological signals.