Fractal methods to analyze ion channel kinetics

We describe the traditional nonfractal and the new fractal methods used to analyze the currents through ion channels in the cell membrane. We discuss the hidden assumptions used in these methods and how those assumptions lead to different interpretations of the same experimental data. The nonfractal methods assumed that channel proteins have a small number of discrete states separated by fixed energy barriers. The goal was to determine the parameters of the kinetic diagram, which are the number of states, the pathways between them, and the kinetic rate constants of those pathways. The discovery that these data have fractal characteristics suggested that fractal approaches might provide more appropriate tools to analyze and interpret these data. The fractal methods determine the characteristics of the data over a broad range of time scales and how those characteristics depend on the time scale at which they are measured. This is done by using a multiscale method to accurately determine the probability density function over many time scales and by determining how the effective kinetic rate constant, the probability of switching states, depends on the effective time scale at which it is measured. These fractal methods have led to new information about the physical properties of channel proteins in terms of the number of conformational substates, the distribution of energy barriers between those states, and how those energy barriers change with time. The new methods developed from the fractal paradigm shifted the analysis of channel data from determining the parameters of a kinetic diagram to determining the physical properties of channel proteins in terms of the distribution of energy barriers and/or their time dependence. (C) 2001 Academic Press.