Channeling studies in yeast: yeast as a model for channelopathies?

Regulation of the concentration of ions within a cell is mediated by their specific transport and sequestration across cellular membranes. This regulation constitutes a major factor in the maintenance of correct cellular homeostasis, with the transport occurring through the action of a large number of different channel proteins localized to the plasma membrane as well as to various organelles. These ion channels vary in specificity from broad (cationic vs anionic) to highly selective (chloride vs sodium). Mutations in many of these channels result in a large number of human diseases, collectively termed channelopathies. Characterization of many of these channels has been undertaken in a variety of both prokaryotic and eukaryotic organisms. Among these organisms is the budding yeast Saccharomyces cerevisiae. Possessing a fully annotated genome, S. cerevisiae would appear to be an ideal organism in which to study this class of proteins associated to diseases. We have compiled and reviewed a list of yeast ion channels, each possessing a human homolog implicated in a channelopathy. Although yeast has been used for the study of other human disease, it has been under utilized for channelopathy research. The utility of using yeast as a model system for studying ion channels associated to human disease is illustrated using yeast lacking the GEF1 gene product that encodes the human homolog to the chloride channel CLC-3.