Marsh, Donald J3; Wexler, Anthony S3; Brazhe, Alexey4; Postnov, Dmitry E3; Sosnovtseva, Olga5; von Holstein-Rathlou, Niels-Henrik5
1 Neuronal Signalling Lab, Department of Neuroscience and Pharmacology, Faculty of Health and Medical Sciences, Københavns Universitet2 Section of Renal and Vascular Research, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, Københavns Universitet3 unknown4 Neuronal Signalling Lab, Department of Neuroscience and Pharmacology, Faculty of Health and Medical Sciences, Københavns Universitet5 Section of Renal and Vascular Research, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, Københavns Universitet
Tubuloglomerular feedback (TGF) and the myogenic mechanism combine in each nephron to regulate blood flow and glomerular filtration rate. Both mechanisms are non-linear, generate self-sustained oscillations, and interact as their signals converge on arteriolar smooth muscle, forming a regulatory ensemble. Ensembles may synchronize. Smooth muscle cells in the ensemble depolarize periodically, generating electrical signals that propagate along the vascular network. We developed a mathematical model of a nephron-vascular network, with 16 versions of a single nephron model containing representations of both mechanisms in the regulatory ensemble, to examine the effects of network structure on nephron synchronization. Symmetry, as a property of a network, facilitates synchronization. Nephrons received blood from a symmetric electrically conductive vascular tree. Symmetry was created by using identical nephron models at each of the 16 sites, and symmetry breaking by varying nephron length. The symmetric model achieved synchronization of all elements in the network. As little as 1% variation in nephron length caused extensive desynchronization, although synchronization was maintained in small nephron clusters. In-phase synchronization predominated among nephrons separated by 1 or 3 vascular nodes, and anti-phase synchronization for 5 or 7 nodes of separation. Nephron dynamics were irregular and contained low frequency fluctuations. Results are consistent with simultaneous blood flow measurements in multiple nephrons. An interaction between electrical signals propagated through the network to cause synchronization; variation in vascular pressure at vessel bifurcations was a principal cause of desynchronization. The results suggest that the vasculature supplies blood to nephrons but also engages in robust information transfer.
American Journal of Physiology: Renal Physiology, 2012, Vol 304, Issue 1