PARAMETRIC SURVIVAL ANALYSIS FOR GATING KINETICS OF SINGLE POTASSIUM CHANNELS

The gating mechanism and the role of the S4 region in the activation o f Shaker potassium channel was studied by statistical analysis on the wild type and mutant channels which have mutations in the S4 region. S ingle channel currents were recorded with the patch-clamp technique. T he first latency time was analyzed with a parametric survival time reg ression model in which the generalized gamma distribution for the erro r term was assumed. Discrimination among Weibull, gamma, log-normal an d exponential distributions was done with the likelihood ratio test. T he three-parameter generalized gamma distribution was shown to be appr opriate for the data set. The multiple regression function provides th e statistical tests and the quantitative descriptions for the relation ships between the mutations and the voltage dependence of the gating p rocess. These results on statistical relations support the hypothesis that the S4 region plays an important role in sensing transmembrane vo ltage in the gating process, but the gating mechanism is not solely ac counted for by the electrostatic interaction between the charged amino acids and the transmembrane voltage field. This work demonstrates tha t the survival analysis procedures can be useful tools for analyzing n europhysiological signals. (C) 1997 Elsevier Science B.V.