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Workshop 5: The Kidney: Cellular, Tubular, and Vascular Physiology (February 19-23, 2007)

Organizers: Harold Layton, Leon Moore, S. Randall Thomas, and Alan Weinstein

The kidney controls the volume and composition of extracellular fluid and participates in the regulation of blood pressure. Its regulatory function can be understood in terms of the action of resident vascular and epithelial cells. The functional unit of the kidney is the nephron, a long epithelial tubule with attendant vasculature. The kidney processes blood in two basic steps: (1) an ultrafiltrate of blood plasma is formed in specialized vascular capillaries and this fluid enters the renal tubule; (2) the renal tubules transform the ultrafiltrate into urine by means of differential transport of solutes and water through the tubule epithelial cells. These two processes influence each other: the ultrafiltration rate impacts tubule function, and tubule transport can modulate ultrafiltration. Both processes are influenced by body fluid composition, and by neural and hormonal signals that impact on the kidney.

The workshop will focus on the application of mathematical models to elucidate renal function in the context of new experimental methods and data. Physiologists, biophysicists, modelers, and mathematicians will present recent work and discuss current controversies and emerging issues. Topics may include: the regulation of ion channels in renal tubular cells, the regulation of renal hemodynamics, tubular-vascular interactions, new insights into the urine concentrating mechanism, new analytical methods, international computational initiatives, and web-based modeling resources.

Schedule

Monday, February 19
Transport and Signaling
8:30-8:45am Welcome: Avner Friedman
8:45-9:15am Introduction: Harold Layton and Alan Weinstein
9:15-10:00am Peter Jordan: Gating Ion Channels: the Interplay of Structure and Theory
10:00-10:30am Coffee break
10:30-11:15am Benoit Roux
11:15-12:00pm Mark Schumaker: Framework models of ion permeation
12:00-1:30pm Lunch break
1:30-2:15pm Donald Loo: Conformational Dynamics of SGLT1 during Na+/glucose Cotransport
2:15-3:00pm Ian Forster: Electrogenic phosphate transport across renal epithelia: mechanistic insights from experiments and simulations
3:00-3:30pm Coffee break
3:30-4:15pm Alan Weinstein
5:00-7:00pm Reception in MW 724
Tueday, February 20
Transport and Signaling (continued)
8:30-9:15am Thomas Pallone: Vasoactivity and ion channel architecture of the descending vasa recta wall
9:15-10:00am Aurelie Edwards: Modification of Cytosolic Calcium Signaling by Subplasmalemmal Microdomain in Outer Medullary Pericytes
10:00-10:30am Coffee break
10:30-11:15am Sheldon Weinbaum: A new view of the Starling hypothesis and the role of pericytes in the temporal regulation of microvascular exchange
11:15-12:15pm Roundtable symposium: "Modeling transporter function: at what scale, toward what end?" Alan Weinstein (moderator)
12:15-1:45pm Lunch break
Renal Physiome
1:45-2:30pm S. Randall Thomas: Overview of Physiome: QKDB, ontology needs, European & International funding
2:30-3:00pm Peter Harris: The Virtual Kidney: Progress with a 3D anatomical interface, model repository and grid portal for distributed computing
3:00-3:30pm Coffee break
3:30-4:00pm Robert Moss: A Preliminary Model for Studying the Interactions Between Nephrons
4:00-5:00pm Roundtable Symposium: "Big Kidney: The Renal Physiome Project"
Panel: Peter Harris, Leon Moore, and James Schafer (moderator)
Wednesday, February 21
The Urine Concentrating Mechanism and Urea Transport
8:30-9:15am William Dantzler: Three-dimensional functional reconstructions of vascular and tubular structures of inner medulla
9:15-9:45am Thomas Pannabecker: Quantitative Analyses of Nephron and Blood Vessel Architecture in the Renal Inner Medulla
9:45-10:15am Coffee break
10:15-10:45am Erik Christensen: Reconstruction of the mouse nephron and distribution of AQP-1 and UT-A2
10:45-11:15am Lise Bankir: (i) Vascular-tubular relationships in a typical mammalian kidney; (ii) Movie by Reiner Beeuwkes (presented by Lise Bankir): The human kidney
11:15-1:30pm Lunch and poster session: Lise Bankir, Saziye Bayram, Boubacar Benziane, Sylvain Demey, Paula B. Grajdeanu, Nicole Kleinstreuer, James A. Schafer, Kin Lung Siu, and Kay-Pong D. Yip
1:30-2:00am Jeff Sands: Vasopressin regulation of the UT-A1 renal urea transporter
2:00-2:30pm Alan Verkman: Chemical 'knock-out' by small-molecules to probe components of the urinary concentrating system
2:30-3:00pm Mark Knepper: Analysis of cell signaling networks using proteomics methods and ODE-based modeling
3:00-3:30pm Coffee break
3:30-4:00pm Mariano Marcano: Optimization Problems and Algorithms for Mathematical Models of Renal Systems
4:00-5:00pm Roundtable symposium: "Concentrating urine: Knowledge versus Understanding"
Panel: Lise Bankir, Rex Jamison (moderator), and Wilhelm Kriz
Thursday, February 22
Renal Hemodynamics: Macula Densa Transport and Signal Transduction
8:30-8:45am Leon Moore: General introduction
Macula Densa Transport and Signal Transduction: Volker Vallon, Chair
8:45-9:20am Roland Blantz: The Tubular Vascular Relationship of TGF: Is there a Metabolic Contribution to this Connection?
9:20-10:00am Jurgen Schnermann: NKCC2 Isoforms and TGF signaling
10:00-10:30am Coffee break
10:30-11:10am P. Darwin Bell
11:10-12:00pm Roundtable symposium: "Macula densa models: Are we ready yet?"
12:00-1:30pm Lunch break
Mechanisms of Renal Autoregulation: Bill Arenshorst and Branko Braam, Chair
1:30-1:45pm Anil Bidani: Introduction and overview
1:45-2:15pm Roger Loutzenhiser: Systolic Pressure is the Dominant Signal in Autoregulation
2:15-2:45pm Geoffery Williamson: Simulation Studies of Dynamic Models for Renal Autoregulation
2:45-3:15pm Coffee break
3:15-3:45pm Armin Just: Evidence for a third and fourth regulatory mechanism in renal blood flow autoregulation
3:45-4:15pm Ki Chon: Insights from Time-Varying Spectral Analysis
4:15-5:00pm Roundtable symposium : "What's missing: Models and data"
6:00-9:00pm Dinner at the Holiday Inn on the Lane
Friday, February 23
Origins of Hemodynamic Complexity: Will Cupples and Suzanne Ditlevsen
8:30-8:45am William Cupples: Introduction and overview
8:45-9:15am Niels-Henrik Holstein-Rathlou: Synchronization among mechanisms of renal autoregulation is reduced in hypertensive rats
9:15-9:45am Donald Marsh: Routes to chaos in nephron blood flow regulation: nephron synchronization and ensemble formation
9:45-10:15am Coffee break
10:15-10:45am Anita Layton: Multistable Dynamics Mediated by Tubuloglomerular Feedback in a Model of Coupled Nephrons
10:45-11:15am Harold Layton: Harmonics and heterodyning in the tubuloglomerular feedback loop
11:15-11:45am Leon Moore: Sources of complexity in a model of the TGF system
11:45-12:30pm Roundtable symposium