Charge immobilization linked to inactivation in the aggregation model of channel gating

Expected gating currents are derived analytically from a continuous, time-homogenous Markov process formulation of the random behavior of a single aggregation gating site. The concept of aggregation gating involves a voltage-dependent reversible conformational change and a voltage-independent reversible aggregation process. A site is assumed to consist of four hypothetical protein subunits. Based on these assumptions the model is defined by the scheme of transitions between 12 possible site configurations. The model can account for the phenomenon of charge immobilization in asymmetry current data of the voltage-clamped sodium conductance system. It predicts gating currents without a rising phase. A rising phase is obtained, however, if the model is subjected to conventional symmetrical pulse protocols for measuring asymmetry currents in the axon. Novel pulse protocols are given that do not result in a rising phase if applied to the aggregation model. Simplified transition schemes that describe the basic kinetic behavior of the potassium and the sodium conductance system are derived by eliminating transitions of negligible probability from the original scheme.