A Novel Mechanism For Salt and Fluid Transport Across Epithelia

The model proposes that ions bind passively to charged sites on a superficial mucopolysaccharide matrix. The mucopolysaccharide and associated ions is engulfed in small vesicles which coalesce to form larger vesicles where the mucopolysaccharide is broken down to release ions into the cell. The released ions are then transported across the basal membrane by specific pumps (see Fig. 1).

The apical layer of mucopolysaccharide of the model is present in many salt transporting epithelia (Wichard, Komnick & Abel, 1972; Komnick, Rhees & Abel, 1971; Holdich & Ratcliffe, 1970; Van Lennep & Komnick, 1971). Furthermore, mucopolysaccharides on the surface of transporting cells have been shown to absorb ions from hypotonic media (Van Lennep & Komnick, 1971; Wichard & Komnick, 1973). The expected pH sensitivity of an ion binding system has been demonstrated by Garcia-Romeu (1971) in anuran skins where changes of pH cause marked alterations in salt transport. The accumulations of mucopolysaccharide-like material on the apical surface, recorded from the anal papillae of Aedes aegypti when no salt transport is taking place (Edwards, 1979) and from the apical crypts of chlorine cells in the gills of Fundulus (Philpott & Copeland, 1963), may represent cases where salt transport is inhibited but where matrix production continues.

The demonstration of pinocytosis, vesicles and lysosomic activity in association with salt transport is also required by the model. Vesicles have been reported in most transporting epithelia, and in some cases it has been suggested that the surface matrix is engulfed pinocytotically (Holdich & Ratcliffe, 1970; Talbot, Clark & Lawrence, 1972). There is a marked increase in the number of vesicles in toad bladder, when stimulated to transport ; these coalesce to form larger lysosomes in which acid phosphatase activity is demonstrable (Masur et al., 1971).

The activity and localization of inorganic ion pumps should be consistent with the proposed mechanism for salt uptake. In the chloride cells of fish gills the Na+/Ka+ ATPase activity increases as the concentration of the external medium falls, that is, when the need for transport is increased (Kamaky, Ernst & Philpott, 1976a). Na+/Ka⁺ ATPase activity has been shown on both faces of transporting epithelia but the bulk of the activity is located in the basal canaliculi (Karnaky et al. 1976b).

The characteristic arrangement of cell membranes in transporting epithelia are explained in terms of the model. The apical foldings found under conditions of high salt transport act to increase the surface of exposed mucopolysaccharide and thus increase the ion binding per unit area for salt pumps and thus allow transport at a rate equal to the release into the cell. There is no increase in the osmotic gradient into the cell. When the transport rate is low these spaces become expanded forming large lacunae, and thus reducing the surface area and transport capacity of the cell.

Purely salt transporting epithelia have straight lateral borders. Fluid transportion epithelia on the other hand, have elaborate folding of the lateral plasma membranes which often include lateral spaces. Models of fluid transport have located salt pumps the lateral borders and on the membranes bounding the lateral spaces (Wall & Oschman, 1970; Berridge & Gupta, 1968). There is also evidence that water moves around rather than through cell junctions due to the selective permeability of the lateral borders (Hill, 1978; Lane, 1979). Thus in fluid transport, inorganic ions enter the cell by the same route as in salt transport but are then pumped into the lateral space; water enters the lateral space by the paracellular route down its osmotic gradient. The hydrostatic pressure increases and fluid moves down the lateral space; salts are reabsorbed by pumps located on the extensive lateral borders.

The model takes account of the known structure and physiology of transporting cells. By binding ions to a matrix before transport they are osmotically inactive and can be gathered from very low external concentrations without creating a steep osmotic gradient. While using vesicles for transport across the apical membrane and placing salt pumps on the basal and lateral plasma membranes, pumps located on the apical membranes are not precluded. Pumps are probably necessary on all membranes for cell maintenance. Even if bulk movements of salt are in a bound state pumps may be used to alter the composition of fluid transported.

The model does not extend to reversible systems, such as the gills of fish capable of absorbing or secreting ions depending on the external conditions. However, Davis, Jones & Hagler (1979) have shown a vesicle/matrix mechanism for calcium uptake into the cells of the chick duodenum. The vesicle model may have a wider application in both vertebrate and invertebrate transporting epithelia. A critical test of the model will be the degree of ion binding to surface mucopolysaccharides and the rate at which vesicles of this material can be formed.