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This Article Full Text Full Text (PDF) Supplemental Tables All Versions of this Article: 296/4/F751    most recent 90669.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Marsh, D. J. Articles by Holstein-Rathlou, N.-H. Search for Related Content PubMed PubMed Citation Articles by Marsh, D. J. Articles by Holstein-Rathlou, N.-H.

Electrotonic vascular signal conduction and nephron synchronization

¹Department of Molecular Pharmacology, Physiology, and Biotechnology, Brown University, Providence, Rhode Island; ²Department of Physiology and Biophysics, Zilkha Neurogenetic Institute, University of Southern California, Los Angeles, California; ³Department of Physics, Danish Technical University, Lyngby; and ⁴Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark

Submitted 11 November 2008 ; accepted in final form 23 December 2008

Tubuloglomerular feedback (TGF) and the myogenic mechanism control afferent arteriolar diameter in each nephron and regulate blood flow. Both mechanisms generate self-sustained oscillations, the oscillations interact, TGF modulates the frequency and amplitude of the myogenic oscillation, and the oscillations synchronize; a 5:1 frequency ratio is the most frequent. TGF oscillations synchronize in nephron pairs supplied from a common cortical radial artery, as do myogenic oscillations. We propose that electrotonic vascular signal propagation from one juxtaglomerular apparatus interacts with similar signals from other nephrons to produce synchronization. We tested this idea in tubular-vascular preparations from mice. Vascular smooth muscle cells were loaded with a fluorescent voltage-sensitive dye; fluorescence intensity was measured with confocal microscopy. Perfusion of the thick ascending limb activated TGF and depolarized afferent arteriolar smooth muscle cells. The depolarization spread to the cortical radial artery and other afferent arterioles and declined with distance from the perfused juxtaglomerular apparatus, consistent with electrotonic vascular signal propagation. With a mathematical model of two coupled nephrons, we estimated the conductance of nephron coupling by fitting simulated vessel diameters to experimental data. With this value, we simulated nephron pairs to test for synchronization. In single-nephron simulations, the frequency of the TGF oscillation varied with nephron length. Coupling nephrons of different lengths forced TGF frequencies of both pair members to converge to a common value. The myogenic oscillations also synchronized, and the synchronization between the TGF and the myogenic oscillations showed an increased stability against parameter perturbations. Electronic vascular signal propagation is a plausible mechanism for nephron synchronization. Coupling increased the stability of the various oscillations.

renal autoregulation; tubuloglomerular feedback; myogenic mechanism; coupled oscillators; coupled nephrons; stability