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Abstract: PO1978

The Sensitivity of Podocytes to ATP In Vivo Is Distinctly Lower than the Sensitivity of Glomerular Endothelial and Proximal Tubular Cells

Session Information

  • Podocyte Biology
    October 22, 2020 | Location: On-Demand
    Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

  • 1204 Podocyte Biology

Authors

  • Binz, Julia, Department II of Internal Medicine and Center for Molecular Medicine Cologne, University of Cologne, Faculty of Medicine and University Hospital Cologne,, Cologne, NRW, Germany
  • Schermer, Bernhard, Department II of Internal Medicine and Center for Molecular Medicine Cologne, University of Cologne, Faculty of Medicine and University Hospital Cologne,, Cologne, NRW, Germany
  • Benzing, Thomas, Department II of Internal Medicine and Center for Molecular Medicine Cologne, University of Cologne, Faculty of Medicine and University Hospital Cologne,, Cologne, NRW, Germany
  • Hackl, Matthias, Department II of Internal Medicine and Center for Molecular Medicine Cologne, University of Cologne, Faculty of Medicine and University Hospital Cologne,, Cologne, NRW, Germany
Background

ATP signaling is involved in a plethora of pathways, involving damage signaling. Cell culture models as well as experiments on isolated glomeruli indicate that podocytes respond to ATP with a calcium transient. To date a direct effect of ATP on podocyte calcium levels in vivo has not been demonstrated.

Methods

In this study mice expressing GCaMP3 in podocytes (Pod:cre), proximal tubular cells (Pax8:cre) or endothelial cells (Tie2:cre) underwent multiphoton in vivo imaging of the kidney. Mice were anaesthetized, an arterial catheter was placed into the right carotid artery or the aorta and the left kidney was exteriorized. The vasculature was labelled with a 70-kDa dextrane. Different doses of ATP were injected as a bolus via the catheter and dose-dependent calcium transients were monitored.

Results

Our data indicates that even doses of 5 mg/kg ATP did not induce calcium transients in podocytes when injected via a carotid artery catheter, while robust activation of calcium signaling was induced in endothelial and proximal tubular cells with 0.5 mg/kg ATP. Further increasing the ATP dose by injection via an abdominal aortic catheter resulted in a calcium transient in podocytes.

Conclusion

In contrast to endothelial cells and proximal tubular cells, podocytes show a low sensitivity to ATP-mediated calcium signaling. We therefore hypothesize, that the low sensitivity ATP of podocytes is a protection mechanism to avoid calcium signals from filtered ATP.

Funding

  • Government Support - Non-U.S.