Zero-current potentials in a large membrane channel: a simple theory accounts for complex behavior

Flow of ions through large channels is complex because both cations and anions can penetrate and multiple ions can be in the channel at the same time. A modification of the fixed-charge membrane theory of Teorell was reported (Peng, S., E. Blachly-Dyson, M. Forte, and M. Colombini. 1992. Biophys. J. 62:123–135) in which the channel is divided into two compartments: a relatively charged cylindrical shell of solution adjacent to the wall of the pore and a relatively neutral central cylinder of solution. The zero-current (reversal) potential results in current flow in opposite directions in these two compartments. This description accounted rather well for the observed reversal potential changes following site-directed mutations. Here we report the results of systematic tests of this simple theory with the mitochondrial channel, VDAC (isolated from Neurospora crassa), reconstituted into planar phospholipid membranes. The variation of the observed reversal potential with transmembrane activity ratio, ionic strength, ion mobility ratio, and net charge on the wall of the pore are accounted for reasonably well. The Goldman-Hodgkin-Katz theory fails to account for the observations