Stochastic Gating as a Novel Mechanism for Channel Selectivity

An ideal channel, responsible for metabolite fluxes in and out of the cells and cellular compartments, is supposed to be selective for a particular set of molecules only. However, such a channel has to be wide enough to accommodate relatively large metabolites, and, therefore, it allows passage of smaller solutes, for example, sodium, potassium, and chloride ions, thus compromising membrane's barrier function. Here we show that stochastic gating is able to provide a mechanism for the selectivity of wide channels in favor of large metabolites. Specifically, applying our recent theory of the stochastic gating effect on channel-facilitated transport, we demonstrate that under certain conditions gating hinders translocation of fast-diffusing small solutes to a significantly higher degree than that of large solutes that diffuse much slower. We hypothesize that this can be used by Nature to minimize the shunting effect of wide channels with respect to small solutes.