Kinetic modeling of ion conduction in KcsA potassium channel.

KcsA constitutes a potassium channel of known structure that shows both high conduction rates and selectivity among monovalent cations. A kinetic model for ion conduction through this channel that assumes rapid ion transport within the filter has recently been presented by Nelson. In a recent, brief communication, we used the model to provide preliminary explanations to the experimental current-voltage J-V and conductance-concentration g-S curves obtained for a series of monovalent ions (K(+),Tl(+), and Rb(+)). We did not assume rapid ion transport in the calculations, since ion transport within the selectivity filter could be rate limiting for ions other than native K(+). This previous work is now significantly extended to the following experimental problems. First, the outward rectification of the J-V curves in K(+) symmetrical solutions is analyzed using a generalized kinetic model. Second, the J-V and g-S curves for NH(4) (+) are obtained and compared with those of other ions (the NH(4) (+) J-V curve is qualitatively different from those of Rb(+) and Tl(+)). Third, the effects of Na(+) block on K(+) and Rb(+) currents through single KcsA channels are studied and the different blocking behavior is related to the values of the translocation rate constants characteristic of ion transport within the filter. Finally, the significantly decreased K(+) conductance caused by mutation of the wild-type channel is also explained in terms of this rate constant. In order to keep the number of model parameters to a minimum, we do not allow the electrical distance (an empirical parameter of kinetic models that controls the exponential voltage dependence of the dissociation rate) to vary with the ionic species. Without introducing the relatively high number of adjustable parameters of more comprehensive site-based models, we show that ion association to the filter is rate controlling at low concentrations, but ion dissociation from the filter and ion transport within the filter could limit conduction at high concentration. Although some experimental data from other authors were included to allow qualitative comparison with model calculations, the absolute values of the effective rate constants obtained are only tentative. However, the relative changes in these constants needed to explain qualitatively the experiments should be of significance.