Solute uptake through general porins

General diffusion porins are among the few membrane proteins that have been thoroughly investigated by many techniques, including X-ray crystallography, AFM microscopy, computer modeling, electrophysiology and biochemistry. This had led to a good understanding of the process of solute transport per se. However, other aspects of porin function remain enigmatic, such as the molecular basis and physiological relevance of many regulatory processes. After summarizing the most salient structural features, the review provides a description of the techniques used for the functional study of porins. The process of solute transport is presented on the basis of structure-function relationship and modeling studies. Three aspects of regulation are discussed: voltage-dependence, pH sensitivity and modulation by polycations and polyanions. The review ends with a perspective on future porin research, to be targeted at a molecular understanding of the regulatory processes, the deciphering of the physiological context in which these processes take place, and rational drug design.