A theory for the reversal potential V, in a wide, charged ion channel (i.e., with radius comparable to channel length and Debye's length) embedded in a planar membrane is developed. We analyze the influence of a nonuniform channel charge distribution along, the channel axis on V,. The analysis is performed in the framework of the space charge model, which is generalized for axial nonuniform charge distributions. Two kinds of nonhomogeneity are considered: (1) a symmetrical nonhomogeneous distribution when channel charge is uniformly smeared over the inner surface of channel wall, but it does not extend over the whole surface, and (2) an asymmetrical nonhomogeneous distribution corresponding to some part of the total charge uniformly smeared over the channel wall and some other located on one of the channel entrances. Forthe first distribution it is shown that even a small deviation from a uniform distribution leads to a significant change in the reversal potential. In particular, the experimentally observed nonmonotonic behavior of V, for the voltage-dependent anion channel from mitochondria (VDAC) as a function of concentration gradient [Zambrowicz, E. B.; Colombini, M.; Biophys. J. 1993, 65, 1093.] is explained by invoking the axial nonhomogeneity of channel charge. For the second kind of distribution (which resembles that in VDAC closed states) it is shown that the sign and value of the reversal potential depends on the location of the mobile part of the channel charge. Theoretical results are compared with previously reported experimental data for VDAC but they are valid for any charged multiionic channel where the Nernst-Planck formalism can be applied.