Potassium channels constitute the largest family of membrane proteins that determine the activity of neurons. Using the available plethora of functional and structural data, we will elaborate a knowledge-based procedure and a set of rules to provide an estimation of the conductance and gating kinetics regulating ion permeation in the different potassium channels. Different gating mechanisms control the activity of a potassium channel: beside a main gate that can be triggered by ligand binding or variation of the transmembrane voltage, there are two inactivation mechanisms, known as N-type and C-type inactivation, that can modulate the opening probability of the channel. The different gating mechanisms are known to be interdependent and influenced by external factors such as the concentration of permeant and impermeant ions. The neuronal functions are potentially affected by both the entry and exit rates of
the inactivation mechanisms. Our goal is to identify the key elements that determine the gating kinetics of the various potassium channels and to predict the phenotype of a channel based on its sequence and tri-dimensional structure.