Cell Volume Regulation in Nonrenal Epithelia

Abstract

Cell volume regulation occurs in both tight, Na⁺-transporting epithelia (e.g., frog skin) and in leaky, NaCl-transporting epithelia (e.g., amphibian gallbladder). In tight epithelia volume regulation occurs only in response to cell swelling, i.e. only regulatory volume decrease (RVD) is observed, whereas in leaky epithelia cell volume regulation has been observed in response to osmotic challenges that either swell or shrink the cells. In other words, both RVD and regulatory volume increase (RVI) are present. Both volume regulatory responses involve stimulation of ion transport in a polarized fashion: in RVD the response is basolateral KC1 efflux, whereas in RVI it is apical membrane NaCl uptake. The loss of KCl during RVD appears to result in most instances from increases in basolateral electrodiffusive K⁺ and Cl^- permeabilities. In gallbladder, concomitant activation of coupled KCl efflux may also occur. The RVI response includes activation of apical membrane cation (Na⁺/H⁺) and anion (Cl^-/HCO^-₃) exchangers. It is presently unclear whether the net ion fluxes resulting from activation of these transporters, during either RVD or RVI, account for the measured rates of restoration of cell volume. In gallbladder epithelium, RVD is inhibited by agents which disrupt microfilaments or interfere with the Ca²⁺-calmodulin system. These pharmacologic effects are absent in RVI. Some steps in the chain of events resulting in either RVI or RVD have been established, but the signals involved remain largely unknown. There is reason to suspect a role of intracellular pH in the case of RVI and of membrane insertion of transporters in the case of RVD, possibly with causal roles of both intracellular Ca²⁺ and the cytoskeleton in the latter.

Effects of Serosal Hypotonicity and Anion Substitutions on Apical and Basolateral K⁺ Conductances

“…In accord with some previously expressed views [14,16,17,22], we consider that the dilution of the serosal solution produces an osmotic swelling, which is then compensated by the loss of K+ from the epithelial cells through the basolateral membranes. Conse quently, the cells are hyperpolarized and this further entails an increased K+ entry across the apical membrane.…”

“…In deed. it is well known that volume expansion by hypotonicity is followed by a regulatory volume decrease [11][12][13][14], which is mediated by the activation of pathways for KC1 exit. On the other hand, the gluconate-Cb replace ments will induce a persistent cell swelling [10] which might result in steady-state cell volumes larger than those obtained after hy potonicity.…”

“…Most likely, these effects are related to increases in cell volume as a consequence of the large per meability of the serosal membranes to water [ 17] followed by an increase of the basolateral K+ conductance [7,14], Similar changes in cell volume can be achieved by replacements of the impermeable anion gluconate by Cl~ [10], The influence of gluconate-Cl" substitu tions in the basolateral as well as apical bath ing solution on the time course of Isc is illus trated in figure 5. Mean values are summa rized in table 2.…”

“…Studies in several cell types [11][12][13][14][15][16][17] demonstrated that after expo sure to hypotonic solutions, cells initially swell but then return to almost their initial volume. This volume regulatory decrease was attributed to an increase in K+ permeability [11,12], which, in some cell types, was accom panied by the induction of a Cl" conductance [12,14,17], We chose to investigate the effects of hypotonicity on the epithelia of R. temporaria. The K+ pathways in this tissue resemble those in the distal part of the neph ron [18.…”

Cell Volume Regulation in Renal Cortical Cells

“…A link of cell volume and transepi thelial transport has been further observed in extrarenal tissues, as discussed in separate chapters of this issue [Macknight, 1988;Reuss, 1988], Apart from the given examples, the link of cell volume and renal transport regulation has been scarcely explored and certainly deserves special attention in future re search.…”