American journal of physiology. Renal physiology
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Am. J. Physiol. Renal Physiol. · Feb 2011
A mathematical model of the urine concentrating mechanism in the rat renal medulla. I. Formulation and base-case results.
A new, region-based mathematical model of the urine concentrating mechanism of the rat renal medulla was used to investigate the significance of transport and structural properties revealed in anatomic studies. The model simulates preferential interactions among tubules and vessels by representing concentric regions that are centered on a vascular bundle in the outer medulla (OM) and on a collecting duct cluster in the inner medulla (IM). Particularly noteworthy features of this model include highly urea-permeable and water-impermeable segments of the long descending limbs and highly urea-permeable ascending thin limbs. ⋯ Model simulations predict that the interstitial NaCl and urea concentrations in adjoining regions differ substantially in the OM but not in the IM. In the OM, active NaCl transport from thick ascending limbs, at rates inferred from the physiological literature, resulted in a concentrating effect such that the intratubular fluid osmolality of the collecting duct increases ~2.5 times along the OM. As a result of the separation of urea from NaCl and the subsequent mixing of that urea and NaCl in the interstitium and vasculature of the IM, collecting duct fluid osmolality further increases by a factor of ~1.55 along the IM.
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Am. J. Physiol. Renal Physiol. · Feb 2011
EphrinB2 induces pelvic-urethra reflex potentiation via Src kinase-dependent tyrosine phosphorylation of NR2B.
Recently, the role of EphB receptor (EphBR) tyrosine kinase and their ephrinB ligands in pain-related neural plasticity at the spinal cord level have been identified. To test whether Src-family tyrosine kinase-dependent glutamatergic N-methyl-d-aspartate receptor NR2B subunit phosphorylation underlies lumbosacral spinal EphBR activation to mediate pelvic-urethra reflex potentiation, we recorded external urethra sphincter electromyogram reflex activity and analyzed protein expression in the lumbosacral (L(6)-S(2)) dorsal horn in response to intrathecal ephrinB2 injections. ⋯ Pretreatment with PP2 (50 μM, 10 μl it), an Src-family kinase antagonist, reversed the reflex potentiation, as well as Src kinase and NR2B phosphorylation. Together, these results suggest the ephrinB2-dependent EphBR activation, which subsequently provokes Src kinase-mediated N-methyl-d-aspartate receptor NR2B phosphorylation in the lumbosacral dorsal horn, is crucial for the induction of spinal reflex potentiation contributing to the development of visceral pain and/or hyperalgesia in the pelvic area.
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Am. J. Physiol. Renal Physiol. · Feb 2011
A mathematical model of the urine concentrating mechanism in the rat renal medulla. II. Functional implications of three-dimensional architecture.
In a companion study [Layton AT. A mathematical model of the urine concentrating mechanism in the rat renal medulla. I. ⋯ An unexpected finding is that the concentrating capability of this region-based model falls short of the capability of models that have radially homogeneous interstitial fluid at each level of only the inner medulla (IM) or of both the outer medulla and IM, but are otherwise analogous to the region-based model. Nonetheless, model results reveal the functional significance of several aspects of tubular segmentation and heterogeneity: 1) the exclusion of ascending thin limbs that reach into the deep IM from the collecting duct clusters in the upper IM promotes urea cycling within the IM; 2) the high urea permeability of the lower IM thin limb segments allows their tubular fluid urea content to equilibrate with the surrounding interstitium; 3) the aquaporin-1-null terminal descending limb segments prevent water entry and maintain the transepithelial NaCl concentration gradient; 4) a higher thick ascending limb Na(+) active transport rate in the inner stripe augments concentrating capability without a corresponding increase in energy expenditure for transport; 5) active Na(+) reabsorption from the collecting duct elevates its tubular fluid urea concentration. Model calculations predict that these aspects of tubular segmentation and heterogeneity promote effective urine concentrating functions.