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E. Bruce Pitman : Tubuloglomerular Feedback-Mediated Dynamics in Two Coupled Nephrons

Previously, we developed a ``minimal'' dynamic model for the tubuloglomerular feedback (TGF) system in a single, short-looped nephron of the mammalian kidney. In that model, a semilinear hyperbolic partial differential equation was used to represent two fundamental processes of mass transport in the nephron's thick ascending limb (TAL): chloride advection by fluid flow through the TAL lumen and transepithelial chloride transport from the lumen to the interstitium. An empirical function and a time delay were used to relate nephron glomerular filtration rate to the chloride concentration at the macula densa of the TAL. Analysis of the model equations indicated that limit-cycle oscillations (LCO) in nephron fluid flow and chloride concentration can emerge for suffficiently large feedback gain and time delay. In this study, the single-nephron model has been extended to two nephrons, which are coupled through their filtration rates. Explicit analytical conditions were obtained for bifurcation loci corresponding to two special cases: (1) identical time-delays, but differing gains, and (2) identical feedback gain magnitudes, but differing time delays. Similar to the case of a single nephron, the analysis indicates that LCO can emerge in coupled nephrons for sufficiently large gains and delays. However, these LCO may emerge at lower values of the feedback gain, relative to a single (i.e., uncoupled) nephron, or at shorter delays, provided the delays are sufficiently close. These results suggest that, in vivo, if two nephrons are sufficiently similar, then coupling will tend to increase the likelihood of LCO. (In collaboration with Roman M. Zaritski, Leon C. Moore and H. E. Layton)

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