Kidney Week

Abstract: SA-PO1008

Calcium-Dependent Contraction of Renal Tubules

Session Information

• Fluid and Electrolytes: Basic - II
  October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Fluid and Electrolytes

• 901 Fluid and Electrolytes: Basic

Authors

• Svendsen, Samuel L.C., Aarhus University, Aarhus C, Denmark

Samuel L.C. Svendsen,

• Hofherr, Alexis, University of Freiburg - Medical Center, Freiburg im Breisgau, Germany

Alexis Hofherr,

• Kottgen, Michael, University Medical Center Freiburg, Freiburg, Germany

Michael Kottgen,

• Leipziger, Jens G., Aarhus University, Aarhus C, Denmark

Jens G. Leipziger,

Background

Over several years, we have observed, that perfused renal tubules show “odd movements” when exposed to extracellular ATP. Whether this observation was merely an artefact or a relevant biological observation remained elusive. It is well known that renal tubules express a contractile machinery localized closely to the apical membrane. The functionality of this structure is enigmatic. Plate grown kidney cells show a pattern on their apical membrane consistent with active contraction of the luminal membrane domain.
Here we test if isolated perfused renal tubules can contract.

Methods

We measured the effect on tubular diameter in isolated murine thick ascending limbs (TAL), when inducing a cytosolic [Ca²⁺] ([Ca²⁺]_i) increase with uncaging ATP/stimulation of the apical P2Y2 receptors.

Results

Uncaging luminal ATP elicited a marked increase of [Ca²⁺]_i, which could be fully blocked by intracellular Ca²⁺ chelation following BAPTA-AM loading. Remarkably, within 40 seconds following apical P2Y2 receptor stimulation, both the inner and outer diameter of the perfused TAL were significantly reduced. The inner and outer diameter decreased by 0.236µm (SEM ±0.041, n=5) and 0.170 µm (SEM ±0.022, n=5), respectively. This reduction could be largely prevented either blocking the [Ca²⁺]_i increase with BAPTA or by hindering actin-myosin interaction with highly specific antagonists.

Conclusion

We report the remarkable observation that renal tubules in a [Ca²⁺]_i -dependent manner can contract. This suggests that the diameter of renal tubules is a subject to active and acute regulation.

Funding

• Government Support - Non-U.S.