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Urinary tract pacemaker cells: current knowledge and insights from nonrenal pacemaker cells provide a basis for future discovery

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Abstract

Coordinated ureteric peristalsis propels urine from the kidney to the bladder. Cells in the renal pelvis and ureter spontaneously generate and propagate electrical activity to control this process. Recently, c-kit tyrosine kinase and hyperpolarization-activated cyclic nucleotide-gated channel 3 (HCN3) were identified in the upper urinary tract. Both of these proteins are required for coordinated proximal to distal contractions in the ureter. Alterations in pacemaker cell expression are present in multiple congenital kidney diseases, suggesting a functional contribution by these cells to pathologic states. In contrast to gut and heart pacemaker cells, the developmental biology of ureteric pacemaker cells, including cell lineage and signaling mechanisms, is undefined. Here, we review pacemaker cell identify and function in the urinary pelvis and ureter and the control of pacemaker function by Hedgehog-GLI signaling. Next, we highlight current knowledge of gut and heart pacemaker cells that is likely to provide insight into developmental mechanisms that could control urinary pacemaker cells.

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Acknowledgments

This work was supported by grants from the Canadian Institutes of Health Research and Canada Research Chairs Program (to NDR).

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Authors and Affiliations

  1. Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, Peter Gilgan Centre for Research and Learning, 686 Bay Street, Toronto, Ontario, Canada, M5G OA4

    Meghan M. Feeney & Norman D. Rosenblum

  2. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada

    Meghan M. Feeney & Norman D. Rosenblum

  3. Division of Nephrology, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada, M5G 1X8

    Norman D. Rosenblum

  4. Deparment of Physiology, University of Toronto, Toronto, Ontario, Canada

    Norman D. Rosenblum

  5. Deparment of Paediatrics, University of Toronto, Toronto, Ontario, Canada

    Norman D. Rosenblum

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  1. Meghan M. Feeney
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  2. Norman D. Rosenblum
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Correspondence to Norman D. Rosenblum.

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Feeney, M.M., Rosenblum, N.D. Urinary tract pacemaker cells: current knowledge and insights from nonrenal pacemaker cells provide a basis for future discovery. Pediatr Nephrol 29, 629–635 (2014). https://doi.org/10.1007/s00467-013-2631-4

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  • DOI: https://doi.org/10.1007/s00467-013-2631-4

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