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Aquaporins in desert rodent physiology.

Abstract. Desert rodents face a sizeable challenge in maintaining salt and water homeostasis due to their life in an arid environment. A number of their organ systems exhibit functional characteristics that limit water loss above that which occurs in non-desert species under similar conditions. These systems include renal, pulmonary, gastrointestinal, nasal, and skin epithelia. The desert rodent kidney preserves body water by producing a highly concentrated urine that reaches a maximum osmolality nearly three times that of the common laboratory rat. The precise mechanism by which urine is concentrated in any mammal is unknown. Insights into the process may be more apparent in species that produce highly concentrated urine. Aquaporin water channels play a fundamental role in water transport in several desert rodent organ systems. The role of aquaporins in facilitating highly effective water preservation in desert rodents is only beginning to be explored. The organ systems of desert rodents and their associated AQPs are described.

Introduction

The obvious challenge faced by desert rodents, of maintaining salt and water homeostasis in an arid environment, quickly raises questions about the roles that aquaporin water channels (AQPs) might play throughout the body. Renal mechanisms also influence the water-conserving mechanisms of desert rodents. Fluid reabsorption from proximal tubules, descending thin limbs of Henle's loop, and collecting ducts and fluid flows across renal capillary endothelia (the vasa recta) are critical for minimizing urinary water loss from the body. Desert rodents conserve water, in part, by producing highly concentrated urine and very dry feces. These animals can concentrate urine more than 20-fold that of plasma, with urine reaching as high as 9000 mOsm/kg [H.sub.2]O in the Spinifex hopping mouse (MacMillen and Lee, 1967) and the desert mouse possum (Diaz et al., 2001). (Refer to Table 1 for the common and scientific names of rodents discussed in this review.) The white Sprague-Dawley and Munich-Wistar rat strains concentrate urine to about 10 times that of plasma, or 3000 mOsm/kg [H.sub.2]O. In polarized cells that make up the epithelia of renal nephrons, multiple AQPs are expressed in apical or basolateral membranes and they underlie transepithelial water fluxes that are essential in producing a concentrated urine (Fenton and Knepper, 2007; Pannabecker, 2013).

Minimization of evaporative water losses by pulmonary, nasal, and skin epithelia is also a potential mechanism for conserving water in desert rodents. Schmidt-Nielsen and Schmidt-Nielsen (1950, 1951) found that in heteromyids (kangaroo rats and pocket mice), pulmonary evaporative water loss is about 50% that of rat and mouse. While inhabiting burrows with high relative humidity, kangaroo rats experience a substantial reduction in water loss by evaporation. This reduction approaches 75% of the water loss that occurs when they are outside the burrow and which leads to metabolic water production in excess of water lost by evaporation. What are the functions of AQPs in minimizing evaporative water loss in desert rodents?

There have been comparative physiological and anatomical studies of water channels in desert rodents including the kangaroo rat, gerbil, degu, Spinifex hopping mouse, spiny mouse, leaf-eared mouse, and chinchilla. This review focuses on those aquaporins whose expression has been studied primarily in kidney, but includes several other organ systems of desert rodents, and draws some parallels with mouse and rat, generally Sprague-Dawley or Munich-Wistar rat strains.

Organ Systems in Which AQPs Have Been Studied in Desert Rodents

Kidney

Renal medulla. The kidney consists of three distinct zones: the cortex, outer medulla, and inner medulla (Fig. 1). Nephron segments of the renal medulla include the proximal straight tubule, descending and ascending thin limbs of Henle's loop, thick ascending limbs, and the medullary collecting ducts (Fig. 2). All loops of Henle form a 180-degree bend between the descending and ascending segments. Importantly, these loop bends exist at all levels of the inner medulla, and consequently the total number of thin limbs declines exponentially with depth below the outer medulla (Pannabecker et al., 2008; Urity et al., 2012). Collecting ducts descend from cortical distal segments into the outer medulla and continue into and through the inner medulla, where they gradually coalesce into about 6-10 collecting ducts at the tip of the inner medulla. These terminal collecting ducts join the ducts of Bellini, where urine exits the kidney and drains into the ureter. Medullary blood vessels consist of descending and ascending vasa recta and associated capillaries. Descending vasa recta pass from the cortex into the outer medulla, with some vasa recta continuing into the inner medulla. In transit, each descending vas rectum connects to a capillary plexus at any level of the medulla (Pallone et al., 2003; Kim and Pannabecker, 2010; Yuan and Pannabecker, 2010; Pannabecker and Layton, 2014). The capillary plexuses, in turn, connect to ascending venous vasa recta that return plasma to the cortex (Fig. 2).

Production of an osmotic gradient, consisting chiefly of NaCl and urea, and increasing gradually from the cortex to the tip of the inner medulla (Fig. 1), is a fundamental feature of the urine-concentrating mechanism, the chief process by which the kidney preserves fluid and sodium homeostasis in most mammals. At each level of the renal medulla, the osmolality of all nephrons and blood vessels is nearly equivalent to that of the interstitium but is hypertonic to systemic plasma. And at each level, as long as transepithelial water permeability is high enough, the transepithelial osmotic gradient is sufficient to drive fluid reabsorption from the renal tubule lumen into the interstitium; reabsorbed fluid passes into the vasa recta and returns to general circulation. Active [Na.sup.+] reabsorption by the thick ascending limb accounts for the high osmolality of the outer medulla; however, this fact does not explain the high osmolality of the inner medulla, where the steepest increase in the osmotic gradient occurs (Fig. 1). In the production of concentrated urine, there is little or no involvement of active transepithelial [Na.sup.+] reabsorption in the inner medulla (Layton et al., 2004; Layton, 2011; Pannabecker, 2013). Instead, [Na.sup.+] and urea are delivered to the inner medulla through passive reabsorption by the ascending thin limb and collecting duct, respectively, as in the passive mechanism hypothesis of urine concentration (Kokko and Rector, 1972; Stephenson, 1972). Although an outsize degree of active [Na.sup.+] reabsorption by the thick ascending limb of desert rodents may play a role in their capacity to produce a very high urine concentration compared to rats (Doucet et al., 1987; Aw et al., 2014), one must look at the function of inner medullary thin limbs of Henle's loop, collecting ducts, and vasa recta to understand how the inner medullary osmotic gradient is generated.

It was shown more than five decades ago in studies of how the corticomedullary osmotic gradient is generated, that luminal fluid near the bend of thin limbs of Henle's loop of hamster, kangaroo rat, and sand rat is nearly isoosmotic with fluid of the inner medullary interstitium, collecting ducts, and blood vessels at the same level. This process of osmotic equilibration implies that solutes are secreted into the thin limb lumen, water is reabsorbed from the tubule lumen, or both secretion and reabsorption occur (Gottschalk and Mylle, 1959). AQP1 provides a pathway for transepithelial water flows in thin limb segments, but apart from the C1C-K1 chloride channel, the identity of the transport pathways involved with solute secretion and/or reabsorption remains unknown.

The water channel AQP1 is the predominant pathway by which water is reabsorbed from the descending thin limb of Henle's loop in the process of urine concentration (Chou et al., 1999). AQP1 is abundantly expressed in long-looped, descending thin limb segments lying in the outer and inner medullae. However, in a number of mammals where it has been investigated--and possibly in all mammals--the descending thin limb consists of an initial segment that expresses ample AQP1 and a second segment that expresses nearly undetectable AQP1 (Pannabecker, 2012). This AQP1 expression pattern for rodents in general is illustrated in Figure 2. In the lower 40% of the inner medulla, AQP1 expression is relatively low or absent in most descending thin limb segments of the inner medulla of rat, chinchilla, and kangaroo rat, and in descending vasa recta in the lower 40% of the inner medulla of rat and kangaroo rat (Chou et al., 1993; Nielsen et al., 1995; Pannabecker and Dantzler, 2007; Issaian et al., 2012; Urity et al., 2012). AQP 1-positive descending thin limb segments in both rat and chinchilla exhibit substantial transepithelial water permeability, whereas AQP 1-negative descending thin limbs show little or no transepithelial water permeability (Chou and Knepper, 1992; Nawata et al., 2014). Thus, transepithelial water flux greatly influences osmotic equilibration between the lumen of AQP 1-positive segments and the interstitial fluid compartment, but such an equilibration by water flux cannot occur with AQP 1-negative segments. AQP1 expression appears to be a constitutive process because dynamic changes in AQP1 protein expression and water permeability in descending thin limbs with varying hydration states have not been observed or reported in rat or in desert rodents.

In the kangaroo rat, the length of AQP1 expression along the descending thin limb, as a proportion of total inner medullary length, exceeds by 50% the length of AQP1 expression along the rat descending thin limb (Urity et al., 2012). A longer, water-permeable descending thin limb segment possibly leads to a higher degree of water reabsorption in the descending thin limb of kangaroo rat than in that of the rat. This could facilitate osmotic equilibration by water flux between the luminal and interstitial fluid compartments, and lead to higher luminal solute concentration and greater driving force for [Na.sup.+] reabsorption by the ascending thin limb of the kangaroo rat than in rat (Urity et al., 2012). Transepithelial permeability of small solutes such as sodium and urea is very high in AQP 1-negative descending thin limb segments, as shown for rat and chinchilla (Chou and Knepper, 1993; Nawata et al., 2014). Solute secretion into these segments, and not water reabsorption, likely contributes substantially to osmotic equilibration of AQP 1-negative descending segments (Marsh, 1970; Pennell et al., 1974). The collective histotopography of inner medullary, AQP 1-positive and AQP 1-negative descending thin limbs, and vasa recta and their different water permeabilities is important for reducing the fluid load delivered to the deep inner medulla, and is related to the distinct contributions of these segments to the production of the corticomedullary osmotic gradient (Layton et al., 2010).

AQP2 is the primary water pathway for apical water flux in the principal collecting duct cells of rat; AQP3 and AQP4 are the primary basolateral water channels. In the antidiuretic rat, vasopressin increases AQP2 protein trafficking from the intracellular vesicles into the apical membrane, and increases total cellular AQP2 protein expression. Both actions lead to increased water permeability of the apical membrane and higher levels of transepithelial water reabsorption, which concentrate the urine. The terminal inner medullary collecting duct segment (IMCD3) exhibits the greatest transepithelial water permeability of all the collecting duct segments, based on in vitro measurements in the rat (Sands et al., 1987). With in vivo studies, Oliver et al (1982) reported that most of the increase in urine osmolality above isotonicity occurs in the terminal 25% (last 2 mm) of the rat medullary collecting duct. This increase in osmolality was due entirely to water reabsorption, not to solute secretion.

Hypertonicity of the extracellular compartment also serves as a regulator of AQP2 protein expression of medullary collecting duct principal cells, protein trafficking, and water permeability (Lankford et al., 1991; van Balkom et al., 2003; Yui et al., 2013). The transcription factor tonicity-responsive enhancer binding protein (TonEBP) influences regulation of hypertonicity-dependent AQP2 expression in primary cultured collecting duct cells of rat independently of cyclic AMP response element (CRE) activation (Storm et al., 2003). In cortical collecting duct cells derived from mouse (mpkCC[Dc.sub.14]), hypertonicity regulates AQP2 protein abundance independently of vasopressin (Hasler et al., 2005). The transcription factor TonEBP plays a central role in regulating AQP2 expression in mpkCC[Dc.sub.14] cells by enhancing AQP2 gene transcription, which appears to occur independently of vasopressin (Hasler et al., 2006). Hypertonicity can influence preferential apical or basolateral membrane targeting of AQP2 in the rat collecting duct. When renal medullary slices are incubated in hypertonic media, the addition of vasopressin increases the basolateral: AQP2 apical protein expression ratio in the collecting ducts of the outer zone of the inner medulla (van Balkom et al., 2003). It has been hypothesized that following constitutive sorting to the basolateral membrane in rat, vasopressin treatment induces transcytosis of AQP2 to the apical membrane, with a consequent increase in transepithelial water permeability (Yui et al., 2013).

Stable and persistent basolateral AQP2 expression also occurs in the principal cells of the inner medullary collecting duct of kangaroo rat. The AQP2 expression ratio of the basolateral:apical membrane was determined at increasing 1000-[Mu]m intervals beginning from the outer medullaryinner medullary border and continuing to the tip of the papilla (Espineira and Pannabecker, 2014). The basolateral: AQP2 apical ratio in the kangaroo rat was approximately twice as great as that of Sprague-Dawley rats that were either given water ad libitum or were water-restricted. The authors theorized that hypertonicity of the kangaroo rat papilla elevates basolateral:apical AQP2 expression ratios, and perhaps even transepithelial water permeability of the collecting duct, to a greater degree than in the rat. At present, however, there are no published studies of transepithelial water permeability of the collecting ducts in desert rodents.

As indicated above, TonEBP may affect hypertonicity-mediated water reabsorption via collecting duct AQP2 in the mouse. Water deprivation in the Spinifex hopping mouse leads to increased medullary aldose reductase and compatible osmolyte mRNA expression within 3 d, indicative of increased TonEBP activity; this was concurrent with increased urine concentration. The expression of TonEBP mRNA and protein and protein translocation from the cytoplasm into the nucleus of inner medullary collecting ducts in the Spinifex hopping mouse increased after 7 and 14 d of water deprivation (Bartolo and Donald, 2008). One might speculate that hypertonicity and TonEBP play an integrated role in regulating AQP2 expression and water reabsorption of the medullary collecting duct in the Spinifex hopping mouse, as shown for collecting duct cells in mouse (Hasler et al., 2006).

The relative significance of basolateral and apical AQP2 expression (and membrane water permeabilities) of the inner medullary collecting duct in transepithelial water flows needs further clarification. The mechanism by which hypertonicity influences AQP2 targeting in medullary collecting ducts is not known. Investigations into variable AQP2 regulatory pathways in species with high inner medullary interstitial osmolality and high urine concentrating capacity, such as desert rodents, may provide clues about the overall physiological roles of AQP2 membrane sorting pathways.

A number of hormones, including vasopressin and transcription factors, may help in modulating total cell and membrane expression of proteins, such as AQP2 of the kidney collecting duct, that are integral to production of the highly concentrated urine of desert rodents. Vasopressin is expressed in kangaroo rat plasma at two to three times the level in rat (Stallone and Braun, 1988). Comparable or even higher plasma levels than in the water-replete or water-deprived rat have been reported for the gerbil and jerboa (El-Husseini and Haggag, 1974; Baddouri et al., 1984).

In the leaf-eared mouse, a South American desert-dwelling rodent, AQP2, AQP3, and AQP4 renal protein expression was confined to the principal cells of the cortical and inner medullary collecting ducts (Gallardo et al., 2005). In the same study, dehydration of the leaf-eared mouse produced an increase in AQP2 immunolabel and protein abundance, and an increase in AQP3 immunolabel--but to a lesser degree--and produced no change in AQP4 expression.

Studies carried out in free-living degus confirmed that these rodents, as in rats and mice, undergo phenotypic changes in AQP2 expression to cope with environmental water availability (Bozinovic et al., 2003). The whole-body water flux rate in the degu in austral summer was about 25% of the rate seen during austral winter (influx/efflux~1 for animals during both seasons). Greater AQP2 expression of the medullary collecting duct was observed in animals during the austral summer than in austral winter, as was an apparent increase in apical membrane protein expression during the summer. The increased AQP2 expression noted in summer occurred together with an increase in urine osmolality that was about 1.8-fold higher than in winter. One caveat of that study is the possibility that AQP2 expression levels may vary along the corticomedullary axis of the medulla regardless of season, potentially confounding the conclusions. As collecting ducts descend toward the papilla tip, their diameters increase substantially, providing a method to estimate the position of tissue slices obtained from various levels along the corticomedullary axis. Future studies of AQP2 expression at precise axial zones along the length of individual ducts for both summer and winter animals may be informative.

AQP4 protein is expressed in basolateral membranes of mouse and rat principal cells of the collecting duct, and in the S3 segments of mouse proximal tubules but not in those of rat (Frigeri et al., 1995; van Hoek et al., 2000). The kangaroo rat exhibits a quite different pattern of AQP4 expression from that seen in both mouse and rat. While AQP4 mRNA is expressed in the collecting ducts and S3 segments of the proximal tubules of kangaroo rat, AQP4 protein is not expressed in either location or in any part of this animal's kidney (Huang et al., 2001). Renal expression of AQP4 protein in the kangaroo rat kidney is apparently down-regulated at the transcriptional or translational level. A dominant role for AQP4 in basolateral membrane water flux in the mouse urine concentrating mechanism appears unlikely. Even though transepithelial water permeability of the collecting duct of AQP4-knockout mouse (only collecting duct segments from the outer third of the inner medulla were tested) is reduced four-fold from those of wild-type animals (Chou et al., 1998), urine osmolality is reduced from wild-type by only about 20%-25% at most, either with or without 36-h water deprivation (Chou et al., 1998; van Hoek et al., 2000). Because AQP4 is absent from the kangaroo rat kidney altogether, AQP4 clearly is not required for urine concentration in kangaroo rat kidney, and one or more different aquaporins may provide a pathway for basolateral water flux. While AQP4 may provide a significant pathway for water flux across the basolateral membrane of the mouse collecting duct, its role in integrative physiology of the mouse urine concentrating mechanism remains poorly understood.

The kidney of the spiny mouse, a desert-adapted rodent, exhibits efficient mechanisms for filtering and excreting high salt concentrations (Dickinson et al., 2007). When the spiny mouse is placed on a high sodium chloride diet, free water reabsorption exceeds that of the equivalent-sized C57BL/6 mouse by almost 40%. Water balance under normal conditions is similar for both species; however, with a high salt load the spiny mouse maintains its urine concentration but the C57BL/6 mouse does not. The spiny mouse is thought to express a greater number of water channels in the proximal tubule (aquaporin 1-7) and/or collecting duct (aquaporin 2, 3, 4) than the C57BL/6 mouse, allowing greater water reabsorption and higher urine concentration (Dickinson et al., 2007). The ability of the spiny mouse to tolerate a larger increase in plasma osmolality than the C57BL/6 mouse is one way in which this species adapts to increased sodium chloride intake. Other adaptations may include significant variations in circulating and renal concentrations of renin, vasopressin, and angiotensin II; kidney architecture; and intrarenal hemodynamics (Dickinson et al., 2005).

Gastrointestinal tract

Multiple anatomical specializations exist for increasing the small and large intestinal surface area of desert rodents above that of similar-sized mesic species. These include longer intestinal length and mucosal folding, which lead to enhanced water and nutrient absorption in the gastrointestinal tract (Buret et al., 1993; Murray et al., 1995). Thus, fecal water content may be significantly reduced in xeric compared to mesic species as a result of a higher degree of colonic water absorption (Degen, 1997).

Colon. Water flux across the colon epithelium is thought to occur by water channels located in the basolateral and apical membranes and, to some degree, through the paracellular pathway (Kunzelmann and Mall, 2002). Water is absorbed against a relatively high osmotic gradient that is produced by high, effective osmolality of feces. [Na.sup.+] and [Cl.sup.-] are the principal electrolytes generating the transepithelial osmotic gradient that drives fluid absorption in the colon. The degu is capable of producing very dehydrated feces. Water absorption across the degu colon was twice that of water absorption across the rat colon; it was inhibited with the mercurial agent p-chloromercuribenzenesulfonic acid (a known AQP1 antagonist); and it was unaffected by water deprivation (Gallardo et al., 2001, 2002). Distribution of aquaporins in the colon of the degu was studied to determine which aquaporins might contribute to water absorption (Gallardo et al., 2002). AQP1 was shown by immunohistochemistry to reside in the basolateral and apical membranes of surface-absorptive and crypt epithelial cells. AQP2 was not detected in cells of the colon, in contrast to positive expression in rat colon (Gallardo et al., 2001). Detectable AQP3 was absent from the epithelium, but it was found in a subepithelial fibroblast layer, pericryptal cells, and muscularis mucosae. In contrast, in the rat colon AQP3 was expressed in basolateral membranes of villus epithelial cells (Frigeri et al., 1995). AQP8 was expressed in cytoplasm of the enterocytes of surface colon. Ten-day water restriction did not modify the amount, or cellular distribution, of AQPs 1, 3, or 8. AQP3 may represent an adaptation in desert rodents that importantly affects colon fluid reabsorption (Gallardo et al., 2001).

Gastric gland. AQP4 is abundantly expressed in gastric gland pariet al cells of kangaroo rats and other rodents, suggesting a function for AQP4 in gastric acid secretion (Huang et al., 2001). Two AQP4 splice variants (M1-AQP4 and M23-AQP4) are expressed in rodent gastric glands, forming heterotetramers of individual 34- and 32-kDa functional units in native tissue. On freeze-fracture microscopy, AQP4 forms orthogonal arrays of intramembranous particles (OAPs) in the M23-AQP4 variant. This variant exhibits substantially higher osmotic water permeability than the M1-AQP4 form (Silberstein et al., 2004). OAPs are absent in gastric pariet al cells of mouse and kangaroo rat (Silberstein et al., 2004). Therefore, M1-AQP4 is apparently the major form present in these species. OAPs are abundantly co-expressed with AQP4 in Sprague-Dawley rat and Brattleboro rat (i.e., a rat strain that does not produce endogenous vasopressin) (Nielsen et al., 2002). It is not known why water permeability is higher when AQPs are organized into OAPs than when they are not so arrayed (Wolburg et al., 2011). The role of water flux in the pariet al cell via AQP4 is poorly understood. Perfusion studies of water permeability of isolated gastric glands of rat, mouse, and kangaroo rat should help to clarify its function.

Ear and nasal

Inner ear. The inner ear consists of two primary extracellular fluid compartments, the perilymph and the endolymph. The apical face of the sensory cells is bathed by endolymph. The chief cation of endolymph is [K.sup.+] and the chief cation of perilymph is [Na.sup.+]. Thus, a steep electrochemical gradient exists across the single cell layer epithelium that separates the two compartments. At least nine AQPs have been identified in various membranes of the inner ear, where they are considered to help in regulating perilymph and endolymph volume (Eckhard et al., 2012; Nevoux et al., 2014). As with the kidney of desert rodents, which faces powerful evolutionary forces for optimizing water flows to maintain normal function, in the inner ear of these animals it is reasonable to speculate that, in the inner ear of these animals, AQP expression and function similarly lead to optimizing water fluxes. In fact, one may predict that the function of these AQPs will be more apparent in the organs of animals that inhabit extreme arid conditions.

Cochlea. AQP1 expression was observed by immunohisto-chemistry in the cochlea of Mongolian gerbil, specifically in type III and type IV fibrocytes, mesenchymal cells lining the bony otic capsule of the perilymphatic space, and fibrocytes in the spiral limbus. Label intensity in the gerbil was weaker than in the CBA/JNCrj mouse and Hartley guinea pig (Miyabe et al., 2002). Stankovic et al. (1995) had previously shown comparable AQP1 expression patterns in guinea pig inner ear. They noted that, because AQP1 is expressed only in cells that are not epithelial, AQP1 is not involved with transepithelial fluid exchange in the inner ear (Stankovic et al., 1995). AQP4 immunolabel was seen in the supporting cells of the cochlea and in some interdental cells of gerbil. However, although AQP4 was found in root cells of guinea pig cochlea, no detectable AQP4 immunoreactivity was seen in root cells of Mongolian gerbil and mouse (Miyabe et al., 2002). AQP4 expression in the cochlea is essential for normal hearing in mice (Li and Verkman, 2001). In the rat, all isoforms of AQP4 are found in OAPs in the basolateral domains of cochlear duct supporting cells, indicating that AQP4 plays a significant role in maintaining water homeostasis in auditory sensory transduction in the cochlea (Hirt et al., 2011).

It is notable that kangaroo rats and other desert rodents possess high auditory sensitivity, a characteristic that may enhance the ability of these species to detect and evade predators. It is reasonable to speculate that the presence and/or absence of AQPs may influence adaptations that enhance hearing sensitivity in desert rodents. Adaptations might include synergistic roles for AQPs and solute transporters that regulate the volume of perilymph and endolymph fluid (Eckhard et al., 2012; Nevoux et al., 2014). An anatomical study of structural specializations of the gerbil middle and inner ear found a high correlation with auditory sensitivity, with the degree of specialization increasing with increasingly arid environments. This finding supports the view that structure-function adaptations in the ear affect hearing sensitivity in desert rodents (Lay, 1972).

Nasal passage. In the degu, AQP1 is expressed throughout the subepithelial vascular network, but it has not been detected in olfactory or non-olfactory epithelial cells (Gallardo et al., 2008). AQP2 and AQP4 also were not found in these cells.

Perspective

The few studies that have been conducted in AQP protein expression in the kidney of kangaroo rat and other desert rodents suggest that future research on the pathways of transmembrane and/or transepithelial water flows across medullary collecting duct cells is likely to offer new insights into cellular roles and regulation of AQPs as well as the urine concentrating mechanism. AQP patterns of expression in organs of desert rodents do not always follow patterns of expression in rat and mouse. For example, AQP4, which is expressed in rat kidney, is absent in kangaroo rat kidney. AQP2, which is expressed in rat colon, is absent in the degu colon. In the kangaroo rat kidney, another AQP, e.g., AQP2, may play a supporting role in facilitating water permeability of the basolateral membrane of the collecting duct (Espineira and Pannabecker, 2014). Similarly, another AQP may fulfill the role of the AQP2 in the degu colon. Genomic and transcriptomic studies of osmoregulatory genes in the kangaroo rat have demonstrated the potential for these technologies to identify genes that are positively selected for in desert-adapted rodent species (Marra and DeWoody, 2014; Marra et al., 2014). With these technologies, future studies of water-stressed individuals may provide insights into the function of aquaporins in various organ systems.

Two desert rodent organ systems for which AQPs have not been reported include the integumentary and nervous systems. Although ventilatory evaporative water loss is significantly higher in arid species than non-arid species, one study showed that most water loss is cutaneous in the kangaroo rat (Tracy and Walsberg, 2000). The hydration status of the stratum corneum, the most superficial layer of skin, is an important determinant of the barrier function of skin. AQP3 is thought to aid in reducing evaporative water loss and desiccation of the stratum corneum and/or dissipation of water gradients in the epidermal keratinocyte layer (Ma et al., 2002). AQP3 null mice exhibited a more than four-fold reduction in transepidermal water permeability than wild-type mice. Future studies of water transport in the integument of desert rodents may identify an important role for AQP3.

AQPs1, 4, and 9 have been localized to the rat brain and AQP1 to the choroid plexus. In rat, AQP4 is expressed in astrocytes, ependymal cells, and the hypothalamus. AQP4 is involved with [K.sup.+] uptake and release by astrocytes, glial cell migration, glial scarring, and astrocyte-to-astrocyte communication. AQP4 also features in various pathophysiologies; it may serve as an osmosensor that participates in changes in cell volume in the face of concentration gradients (Yool, 2007; Iacovetta et al., 2012). AQP4 is expressed in the astroglial cells of kangaroo rat brain (Huang et al., 2001). The wide range of potential AQP4 osmotic functions in brain and interactions with ion channels, especially the Kir channel, suggests that potentially important insights may be obtained through the study of AQP4 in the brain and sensory systems of desert rodents (Nagelhus and Ottersen, 2013).

Acknowledgments

This research was supported by the National Science Foundation IOS-0952885, DMS/NIGMS-1263943, and by the National Institutes of Health: National Institute of Diabetes and Digestive and Kidney Diseases, DK08333.

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THOMAS L. PANNABECKER (*)

Department of Physiology, AHSC 4128, University of Arizona Health Sciences Center, 1501 N. Campbell Avenue, Tucson, Arizona 85724-5051

Received 11 January 2015; accepted 22 February 2015.

(*) To whom correspondence should be addressed. E-mail: pannabec@email.arizona.edu

Table 1
Common and scientific names and habitat of xeric and mesic rodent
species discussed in the review

Common Name                Scientific Name                Habitat(*)

Chinchilla                 Chinchilla lanigera             Xeric
Degu                       Octodon degus                   Xeric
Desert mouse possum        Thylamys pusilla                Xeric
Gerbil                     Gerbillus gerbillus             Xeric
Golden hamster             Mesocricetus auratus            Mesic
Guinea pig                 Cavia porcellus                 Mesic
Jerboa                     Jaculus orientalis              Xeric
Kangaroo rat               Dipodomys sp.                   Xeric
Leaf-eared mouse           Phyllotis darwini               Xeric
Mouse                      Mus sp.                         Mesic
Pocket mouse               Perognathus sp.                 Xeric
Rat                        Rattus rattus                   Mesic
Sand rat                   Psammomys obesus                Xeric
Spinifex hopping mouse     Notomys alexis                  Xeric
Spiny mouse                Acomys cahirinus                Xeric

(*) Habitat types are from Beuchat, 1996.
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Date:Aug 1, 2015
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