Immunohistochemical study of a rat membrane protein which induces a selective potassium permeation: Its localization in the apical membrane portion of epithelial cells

We previously reported a novel rat membrane protein that exhibits a voltage-dependent potassium channel activity on the basis of molecular cloning combined with an electrophysiological assay. This protein, termed I(sK) protein, is small and different from the conventional potassium channel proteins but induces selective permeation of potassium ions on its expression in Xenopus oocytes. In this investigation, we examined cellular localization of rat I(sK) protein by preparing three different types of antibody that specifically reacts with a distinct part of rat I(sK) protein. Immunohistochemical analysis using these antibody preparations demonstrated that rat I(sK) protein is confined to the apical membrane portion of epithelial cells in the proximal tubule of the kidney, the submandibular duct and the uterine endometrium. The observed tissue distribution of rat I(sK) protein was consistent with that of the I(sK) protein mRNA determined by blot hybridization analysis. In epithelial cells, the sodium, potassium-ATPase pump in the basolateral membrane generates a sodium gradient across the epithelial cell and allows sodium ions to enter the cell through the apical membrane. Thus, taking into account the cellular localization of the I(sK) protein, together with its electrophysiological properties, we discussed a possible function of the I(sK) protein, namely that this protein is involved in potassium permeation in the apical membrane of epithelial cells through the depolarizing effect of sodium entry.