In vivo, cells are immersed in an extracellular solution that contains a variety of bioactive substances including ions and water. Classical electrophysiological analyses of epithelial cells in the stomach and small intestine have revealed that within a distance of several hundred micrometers above their apical plasma membrane, lies an extracellular layer that shows ion concentration gradients undetectable in the bulk phase. This “unstirred layer”, which contains stagnant solutes, may also exist between the bulk extracellular solution and membranes of other cells in an organism and may show different properties. On the other hand, an earlier study using a bacterial planar membrane indicated that H+ released from a transporter migrates in the horizontal direction along the membrane surface much faster than it diffuses vertically toward the extracellular space. This result implies that between the membrane surface and unstirred layer, there is a “nanointerface” that has unique ionic dynamics. Advanced technologies have revealed that the nanointerface on artificial membranes possibly harbors a highly ordered assembly of water molecules. In general, hydrogen bonds are involved in formation of the ordered water structure and can mediate rapid transfer of H+ between neighboring molecules. This description may match the phenomenon on the bacterial membrane. A recent study has suggested that water molecules in the nanointerface regulate the gating of K+ channels. Here, the region comprising the unstirred layer and nanointerface is defined as the interphase between the plasma membrane and bulk extracellular solution (iMES). This article briefly describes the physicochemical properties of ions and water in the iMES and their physiological significance. We also describe the methodologies that are currently used or will be applicable to the interphase research.
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