Epithelial transport in The Journal of General Physiology

Abstract

Epithelia define the boundaries of the body and often transfer solutes and water from outside to inside (absorption) or from inside to outside (secretion). Those processes involve dual plasma membranes with different transport components that interact with each other. Understanding those functions has entailed breaking down the problem to analyze properties of individual membranes (apical vs. basolateral) and individual transport proteins. It also requires understanding of how those components interact and how they are regulated. This article outlines the modern history of this research as reflected by publications in The Journal of General Physiology.

Figure 1.

H₂O movement through cells of Nitella. (Top) Device for measuring fluid movement. A, Half of a single cell immersed in L; B, half of a single cell immersed in R; C, seal separating L and R; L, left aqueous compartment; R, right aqueous compartment. The compartments were insulated with a rubber pencil eraser or a piece of cork, anticipating later development of sucrose–gap preparations. (Bottom) Time course of movement of water from compartment L to R. The distance on the y axis indicates the movement of the water meniscus in the narrow neck of the capillary in compartment L. Curve 1 shows movement from L to R when the fluid in R is switched from H₂O to 0.4 M sucrose with distilled H₂O in L. Curve 2 shows movement in the reverse direction when solution R is replaced with 0.3 M sucrose, showing water flows from a more concentrated compartment to a more dilute compartment. In curve 3, compartment R is replaced with distilled water, bringing the system back to its original state. From Osterhout (1949).

Figure 2.

Epithelial Na⁺ channels in absorptive epithelia. (A) Short-circuit current across the toad urinary bladder and its dependence on Na⁺ and oxidative metabolism are shown. The short-circuit current under normal conditions was equal to the net flux of Na measured with Na²² and Na²⁴. Transport was stimulated by oxytocin or vasopressin and was enhanced in the presence of O₂. From Leaf et al. (1958). (B) Flux-ratio analysis of Na⁺ permeation in frog skin. The value n′ = 1 is consistent with single-ion permeation through channels. From Benos et al. (1983). (C) Dependence of Na⁺ channel activity on aldosterone in rat collecting duct. From Pácha et al. (1993). (D) Conduction through WT ENaC and channels with point mutations in the putative selectivity filter. The WT channel is almost perfectly selective for Na⁺, rather than K⁺, whereas mutations in the second transmembrane domain of the α subunit confer conduction of K⁺. From Kellenberger et al. (2001).

Figure 3.

Control of epithelial fluid secretion. (A) Incorporation of [³²P]phosphatidic acid in goose nasal salt gland in response to a secretagogue. From (Hokin et al., 1960). (B) Control of airway surface liquid in cultured lung epithelial cells from healthy subjects (NL) and from patients with cystic fibrosis (CF). In CF or in the presence of bumetanide, a drug that blocks Cl⁻ entry into the cells, the height of the surface layer is diminished. From Tarran et al. (2006). (C) Gating of CFTR by ATP. From Vergani et al. (2003). (D) Effect of specific negative charges in the outer mouth of the CFTR pore on channel conductance. From Aubin and Linsdell (2006).

Figure 4.

Sodium-glucose cotransport. (A) The effect of a nonmetabolizable glucose analogue on Na⁺ transport (short-circuit current) by rabbit ileum. (B) Cell model of Na-dependent glucose transport. From Schultz and Zalusky (1964). (C) Effect of sugar on voltage-dependent protein conformational changes in SGLT1, measured with a fluorescent label. αMDG, α-methyl-d-glucopyranoside. From Loo et al. (2006). (D) Structure-based kinetic model of sodium-glucose transport. From Longpré et al. (2012).

Figure 5.

Isotonic fluid transport. (A) Solute and water transport in a rat ileum. The dashed line indicates the relationship for identical osmolarities of absorbed fluid and that of the luminal medium. From Curran and Solomon (1957). (B) “Standing-gradient” model to explain isotonic transport. The model postulates that interspaces between cells contain hypertonic fluid with the osmolarity decreasing from the tight junction to the interstitial space. From Diamond and Bossert (1967). (C) Simulation of isotonic fluid transport with a uniformly elevated osmolarity in the interspace. From Sackin and Boulpaep (1975). (D) Model of isotonic fluid transport using Na⁺ recirculation across the basal and lateral membranes. From Larsen et al. (2000).

Figure 6.

Measurements of epithelial water permeability. (A) Changes in cell volume of Necturus gall bladder in response to hypertonic challenge using an optical technique. From Persson and Spring (1982). (B) Similar changes measured with an intracellular microelectrode sensor. Hyper, hypertonic. From Cotton et al. (1989). (C) Measurement of Pf/Pd in toad urinary bladder stimulated with ADH or cAMP, or doped with the ionophore amphotericin B. From Levine et al. (1984). (D) Measurement of H₂O permeability of endosomes isolated from toad urinary bladders with different pretreatments showing high H₂O permeability in these organelles. Br-cAMP, 8-bromoadenosine 3′,5′-cyclic monophosphate. From Shi et al. (1990).