From TER to trans- and paracellular resistance: lessons from impedance spectroscopy.

In epithelia and endothelia, overall resistance (TER) is determined by all ion-conductive structures, such as membrane channels, tight junctions, and the intercellular space, whereas the epithelial capacitance is due to the hydrophobic phase of the plasma membrane. Impedance means alternating current resistance and, in contrast to ohmic resistance, takes into account that, e.g., capacitors become increasingly conductive with increasing frequency. Impedance spectroscopy uses the association of the capacitance with the transcellular pathway to distinguish between this capacitive pathway and purely conductive components (tight junctions, subepithelium). In detail, one-path impedance spectroscopy distinguishes the resistance of the epithelium from the resistance of subepithelial tissues. Beyond that, two-path impedance spectroscopy allows for the separation of paracellular resistance (governed by tight junctional properties) from transcellular resistance (determined by conductive structures residing in the cell membranes). The present paper reviews the basic principles of these techniques, some historic milestones, as well as recent developments in epithelial physiology.