Basic diagram of pathways for solute and H₂O movements across toad urinary bladder. A: paracellular pathway comprised of tight junction (a) and lateral intercellular space (b). B: cellular pathway comprised of two barriers (apical and basolateral membranes) and three compartments [urinary or mucosal (1), cell (2), and interstitial or serosal (3)]. Normally rate constant k_{1 → 2} for Na⁺ is much greater than k_{2 → 1} so that little backflux of Na⁺ occurs from cell to mucosal medium. Similarly k_{2 → 3}, which represents Na⁺ movement through Na⁺ pump, far exceeds k_{3 → 2}. Thus Na⁺ movement through cellular pathway is effectively unidirectional from urine to interstitial fluid. In this diagram intercellular spaces are presumed to be continuous with and in diffusion equilibrium with bathing media and do not constitute additional compartment.

Diagram of cross section of epithelial cell layer lining urinary surface of bladder wall. Microvilli on apical plasma membranes of cells are at top. Three epithelial cell types are shown: most frequent cell type is granular cell (GC) with its characteristic dense granules lying below apical plasma membrane; typical flask‐shaped mitochondria‐rich cell (MRC) is shown; and one basal cell (BC) lies just above basal lamina (BL). Omitted are infrequent goblet cells. Site of Na⁺ pumps along basolateral plasma membranes of GC, as localized by ouabain binding, is depicted by short, solid arrows. Beneath basal lamina but not shown in figure would lie submucosa, containing bundles of smooth muscle, collagen fibers, blood vessels, and nerves, lined on its serosal surface by simple serosa.

Tracings of mucosal surfaces of Dominican (A) and Colombian (B) toad urinary bladders showing contribution of three cell types to topology. Tracings are of cell profiles visualized by differential interference‐contrast microscopy. Mitochondria‐rich cells are indicated by enclosed circles, goblet cells are shown as circles, and granular cells (great majority) are indicated by polygons. Colombian toad bladders (B) contain many more mitochondria‐rich cells. Distribution of mitochondria‐rich cells among granular cells in Dominican toad bladder (A) has no reproducible pattern. Effective magnification, × 330.

Effect of K⁺‐free serosal medium, with or without 10⁻²M ouabain, on short‐circuit current of paired hemibladders. Solid line, K⁺‐free Na⁺ Ringer's + 10⁻²M ouabain, serosa; dashed line, K⁺‐free Na⁺ Ringer's, serosa. Hemibladders, bathed throughout on mucosal surface with Na⁺ Ringer's, were initially washed five times with K⁺‐free media. Ouabain was added to appropriate solution after last wash. Therefore, initial response to K⁺‐free medium is seen before exposure to ouabain, which produced immediate inhibition of short‐circuit current.

Electrical circuit analog for transepithelial Na⁺ transport across toad urinary bladder under steady‐state conditions. M, S, C, mucosal and serosal solutions and cell interior, respectively; R_M, R_B, and R_L, electrical resistances of apical (mucosal), basolateral, and paracellular (leak) barriers, respectively, E_M, E driving forces for Na⁺ movement across two plasma membranes (E_M = E_Na, the Nernst potential for Na⁺ across apical membrane). In this diagram, both bathing media have same composition. Therefore, it is assumed that no diffusion potentials exist within paracellular pathway. Analysis of circuit analog allows derivation of expressions for transmembrane electrical potential of the apical (Ψ_mc) and basolateral (Ψ_cs) membranes and for transepithelial electrical potentials (Ψ_ms):More complex representations are required if more than one ionic species carries current through cellular pathway, if solutions of differing composition bathe both surfaces of tissue, or under non‐steady‐state conditions.

Relationship between mucosal Na⁺ concentration and current generated by pump (I_p) in nystatin‐treated hemibladders. Solid line represents best fit to points using equation 152 where I_max is maximum current generated by pump and K_m is an arbitrary dissociation constant. Vertical lines represent SEM when greater than symbol (n = 7).

Relationships between membrane ion permeabilities and membrane potentials under short‐circuit conditions calculated using modified Goldman‐Hodgkin‐Katz equation (see equation 7) and typical cell ion concentrations estimated by electron microprobe analysis (Table 2). A: effect on membrane potential (ΔΨ) of 3Na⁺:2 K⁺ rheogenic pump (○) compared with electroneutral pump (•), where n indicates the pump ratio with different ratios of P_Na+ P_K−, and P_Cl−P_K+ = 0.05 or 0.50. B: effect on ΔΨ of variations in P_Cl+ P_K+ with P_Na+:P_K+ = 0.10 (▵) or 0.3 (▴) (pump ratio 3Na⁺:2K⁺).

Relationships between membrane potentials (ΔΨ), membrane conductance for Na⁺ (•) and K⁺ (○), and ratios g_Na+:g_K+ (▴) and P_Na+:P_K+ (▪) under short‐circuit conditions, calculated from steady‐state values for transepithelial Na⁺ transport and typical cell ion concentrations.

Measured electrical (ΔΨ) and calculated chemical (E) and electrochemical potentials (Δμ) (expressed in mV) across toad bladder epithelial cell apical (a) and basolateral (bl) plasma membranes under open‐circuit conditions. Values used for membrane potentials are apical membrane, −31 mV; basolateral membrane, +63 mV 93. Equilibrium potentials for Na⁺, K⁺, and Cl⁻ calculated from cell concentrations derived from electron microprobe data (Table 2). Positive values represent driving forces across apical membranes in direction from medium to cell (m → c) and across basolateral membranes in direction from cell to medium (c → s).

Diagram of Na⁺ and H₂O transport across toad urinary bladder epithelial cells under open‐circuit conditions with dilute urine. I: postulated linkage through gap junctions between granular and basal cells; in this example, for Na⁺. II: pathways for Na⁺ transport across cells, including postulated cotransporter for Cl⁻ and net Cl⁻ movement through paracellular pathway. III: consequences, for both H₂O and Na⁺ transport, of occupancy of receptors on basolateral membrane by ADH. There are additional active apical membrane Na⁺ channels, basolateral membrane pump units, and K⁺ channels, together with insertion into apical membrane of vesicles containing H₂O channels. This results in net flow of H₂O from mucosa to serosa as consequence of osmotic gradient.