A parallel path model forNecturus proximal tubule

Abstract

Summary. A parallel path model based on the principles of nonequilibrium thermodynamics was developed for the Necturus proximal tubule. The cellular path was represented as a luminal membrane followed by an irreversible active NaC1 transport system in the peritubular barrier. The shunt pathway was described as three "coarse"' barriers in series: tight junction, lateral intercellular spaces, and basement membrane with connective tissue. Volume and solute flows were predicted by the model equations as a function of applied electric current. Variations of the model parameters revealed the quantitative importance of the shunt path properties and the relative insensitivity of epithelial transport to changes in most cell parameters. Circulation of electric current and solute within the epithelium were shown to significantly influence the bahavior of the tubule in the presence of an electric field. Values for all transport parameters of the shunt path and epithelium were calculated and compared with available experimental evidence. Volume flow and electric currents predicted by the model compared favorably with experimental observations.A new model for the renal proximal tubule is presented in an attempt to explain the results of the preceeding paper [34]. The proximal tubule is represented as a parallel path system in which one path (the extracellular) is composed of barriers in series. Previous investigators have suggested the possibility of fluid and ion flows through the tight junctions and extracellular shunt path. Bentzel et al. [8] proposed a tight junction path in parallel with the cell luminal membrane on the basis of fluid conductance and anatomical measurements. Boulpaep [ 11 ] put forth an analogous concept for ion permeation based on electrical measurements of the relative resistance of the epithelium and individual cell membranes. Many authors have since emphasized the importance of the extracellular shunt path in determining epithelial properties [13, 18 -20, 29, 31, 45]. Models for such a parallel path system in the rat ileum [14] and gallbladder [3] were not in a form in which my results could be evaluated. The model presented here is a specific application of the

Current-induced voltage transients inNecturus proximal tubule

“…This does not imply that the spontaneous transepithelial PD is normally generated by EMFshunt but rather that changes in 1v are more readily achieved by alterations in that electromotive force. In the intestine [11,20] and in the proximal tubule [22] EMFshunt actually is in the opposite direction to the normally observed V and opposes the PD spontaneously developed by EMFceH. The analogue also indicates that the peritubular membrane PD would be influenced only to a small extent by alterations in EMFshunt alone.…”

“…c* was calculated from the liquid junction potential of two NaC1 solutions separated by a barrier. The fluid volume thus determined is a function of the transference numbers of the barrier and for the two cases using the transference numbers for the tight junction [22] is: control 0.4 x 10-5 cm a and volume expanded 0.55 x 10 -5 cm 3. The anatomic volume of the inter- space is about twice as large as this estimate [22,25] suggesting that only a portion of this space is involved in determining its electrical properties; however, no other known epithelial compartment is of the appropriate volume.…”

“…Current clamp results were less easily depicted since Jv was a function of the applied current density and the relative resistance of the epithelium. The theoretical basis for determination of volume flow during the application of a constant current or voltage is considered, in detail, in the subsequent paper [22].…”

“…The results which follow indicate that current passage causes alterations in the salt concentrations of the lateral intercellular spaces and that these concentration changes in turn lead to PD transients and volume flows. The information obtained from the analysis of the time course, direction and magnitude of the voltage and resistance transients is used in the second paper of this pair [22] to estimate some of the transport parameters of the epithelium. The conductance and permeability increases which accompany hyperpolarization of the transepithelial PD (increasing luminal negativity) are explained in this and the succeeding paper as the consequences of increasing the width of the lateral intercellular spaces.…”

Effect of medium tonicity on transepithelial H(+)‐HCO3‐fluxes in rat proximal tubule.

“…The model developed by Spring (1973) for the electrophysiological properties of proximal tubule likewise shows that transepithelial resistance is very sensitive to the geometry of lateral intercellular spaces, hypotonicity increasing and hypertonicity decreasing specific wall resistance of this segment. The increase in specific wall resistance observed when tubules were perfused with hypotonic solution (see Fig.…”