Correlated ion flux through parallel pores: application to channel subconductance states

Many ion channels that normally gate fully open or shut have recently been observed occasionally to display well-defined subconductance states with conductances much less than those of the fully open channel. One model of this behavior is a channel consisting of several parallel pores with a strong correlation between the flux in each pore such that, normally, they all conduct together but, under special circumstances, the pores may transfer to a state in which only some of them conduct. This paper introduces a general technique for modeling correlated pores, and explores in detail by computer simulation a particular model based upon electric interaction between the pores. Correlation is obtained when the transient electric field of ions passing through the pores acts upon a common set of ionizable residues of the channel protein, causing transient changes in their effective pK and hence in their charged state. The computed properties of such a correlated parallel pore channel with single occupation of each pore are derived and compared to those predicted for a single pore that can contain more than one ion at a time and also to those predicted for a model pore with fluctuating barriers. Experiments that could distinguish between the present and previous models are listed.