Tubule electrophysiology: from single channels back to the renal epithelium

The "black box" study of the passive and active electrical properties of single barriers in renal tubules has greatly contributed to the understanding of renal ion transport. With the advent of patch-clamp technology, it is feasible to record the ion flow through single channel proteins of the kidney, to infer their ion selectivity, gating properties, open pore conductivity, and to study directly the regulatory domains or sensors that control the gating of renal ion channels. Accordingly, it should be possible to upscale these microscopic parameters and predict the macroscopic membrane properties of renal membranes, using the knowledge of the microscopic single channel current (ij) for ion "j" under a physiologic driving force, the average number of channels in a single membrane patch (N), the open probability of a single channel (P(o)), the incidence of finding a channel in a population of membrane patches (f), and the area of a typical membrane patch (a). The experimental errors in the determination of each of these microscopic parameters are discussed. On the other hand, the macroscopic membrane properties of renal tubule cells cannot be reliably obtained from measurements of whole-cell patch-clamp, because of the polarized distribution of the dissipative electrical properties within a renal cell. The asymmetrical distribution of channel types, channel density and channel kinetics, between the apical and the basolateral membrane, precludes the use of the whole-cell conductance as the macroscopic reference. Instead, classical equivalent circuit analysis of renal epithelia is still necessary to obtain cell membrane parameters that validity represent the ensembles of single channels.