Research ArticleMetabolismNephrology Open Access | 10.1172/jci.insight.190992

Hasan Demirci,1,2,3 Jessica P. Bahena-Lopez,4 Alina Smorodchenko,5 Xiao-Tong Su,4 Jonathan W. Nelson,6 Chao-Ling Yang,4 Joshua N. Curry,4 Xin-Peng Duan,7,8 Wen-Hui Wang,8 Yuliya Sharkovska,9 Ruisheng Liu,10 Duygu Elif Yilmaz,1,11 Catarina Quintanova,12 Katie Emberley,13 Ben Emery,13 Nina Himmerkus,12 Markus Bleich,12 David H. Ellison,4 and Sebastian Bachmann1,2

1Institute of Functional Anatomy and

2Department of Cell Biology and Neurobiology, Charité – Universitätsmedizin Berlin, Berlin, Germany.

3Department of Medical Biology, Faculty of Medicine, Ankara Yildirim Beyazit University, Ankara, Turkey.

4Division of Nephrology and Hypertension, School of Medicine, Oregon Health & Science University, Portland, Oregon, USA.

5Department of Human Medicine, MSB Medical School Berlin, Berlin, Germany.

6Division of Nephrology and Hypertension, Department of Medicine, Keck School of Medicine of University of Southern California, Los Angeles, California, USA.

7Department of Physiology, Xuzhou Medical University, Xuzhou, China.

8Department of Pharmacology, New York Medical College, Valhalla, New York, New York, USA.

9Department of Pediatric Respiratory Medicine and Department for Pediatric Radiology, Charité – Universitätsmedizin Berlin, Berlin, Germany.

10Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, Florida, USA.

11Department of Nephrology and Medical Intensive Care, Charité – Universitätsmedizin Berlin, Berlin, Germany.

12Institute of Physiology, Christian-Albrechts-University, Kiel, Germany.

13Department of Neurology, Jungers Center for Neurosciences Research, Oregon Health & Science University, Portland, Oregon, USA.

Address correspondence to: Sebastian Bachmann, Charité – Universitätsmedizin Berlin, Institut für Zell- und Neuroanatomie, Philippstr. 12, 10115 Berlin. Phone: 49.30.450.528.001; Email: sbachm@charite.de. Or to: David H. Ellison, Division of Nephrology and Hypertension (L334), Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA. Email: ellisond@ohsu.edu.

Authorship note: HD and JPBL contributed equally to this work. DHE and SB are equal corresponding authors.

Find articles by Demirci, H. in: PubMed | Google Scholar |

1Institute of Functional Anatomy and

2Department of Cell Biology and Neurobiology, Charité – Universitätsmedizin Berlin, Berlin, Germany.

3Department of Medical Biology, Faculty of Medicine, Ankara Yildirim Beyazit University, Ankara, Turkey.

4Division of Nephrology and Hypertension, School of Medicine, Oregon Health & Science University, Portland, Oregon, USA.

5Department of Human Medicine, MSB Medical School Berlin, Berlin, Germany.

6Division of Nephrology and Hypertension, Department of Medicine, Keck School of Medicine of University of Southern California, Los Angeles, California, USA.

7Department of Physiology, Xuzhou Medical University, Xuzhou, China.

8Department of Pharmacology, New York Medical College, Valhalla, New York, New York, USA.

9Department of Pediatric Respiratory Medicine and Department for Pediatric Radiology, Charité – Universitätsmedizin Berlin, Berlin, Germany.

10Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, Florida, USA.

11Department of Nephrology and Medical Intensive Care, Charité – Universitätsmedizin Berlin, Berlin, Germany.

12Institute of Physiology, Christian-Albrechts-University, Kiel, Germany.

13Department of Neurology, Jungers Center for Neurosciences Research, Oregon Health & Science University, Portland, Oregon, USA.

Address correspondence to: Sebastian Bachmann, Charité – Universitätsmedizin Berlin, Institut für Zell- und Neuroanatomie, Philippstr. 12, 10115 Berlin. Phone: 49.30.450.528.001; Email: sbachm@charite.de. Or to: David H. Ellison, Division of Nephrology and Hypertension (L334), Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA. Email: ellisond@ohsu.edu.

Authorship note: HD and JPBL contributed equally to this work. DHE and SB are equal corresponding authors.

Find articles by Bahena-Lopez, J. in: PubMed | Google Scholar

1Institute of Functional Anatomy and

2Department of Cell Biology and Neurobiology, Charité – Universitätsmedizin Berlin, Berlin, Germany.

3Department of Medical Biology, Faculty of Medicine, Ankara Yildirim Beyazit University, Ankara, Turkey.

4Division of Nephrology and Hypertension, School of Medicine, Oregon Health & Science University, Portland, Oregon, USA.

5Department of Human Medicine, MSB Medical School Berlin, Berlin, Germany.

6Division of Nephrology and Hypertension, Department of Medicine, Keck School of Medicine of University of Southern California, Los Angeles, California, USA.

7Department of Physiology, Xuzhou Medical University, Xuzhou, China.

8Department of Pharmacology, New York Medical College, Valhalla, New York, New York, USA.

9Department of Pediatric Respiratory Medicine and Department for Pediatric Radiology, Charité – Universitätsmedizin Berlin, Berlin, Germany.

10Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, Florida, USA.

11Department of Nephrology and Medical Intensive Care, Charité – Universitätsmedizin Berlin, Berlin, Germany.

12Institute of Physiology, Christian-Albrechts-University, Kiel, Germany.

13Department of Neurology, Jungers Center for Neurosciences Research, Oregon Health & Science University, Portland, Oregon, USA.

Address correspondence to: Sebastian Bachmann, Charité – Universitätsmedizin Berlin, Institut für Zell- und Neuroanatomie, Philippstr. 12, 10115 Berlin. Phone: 49.30.450.528.001; Email: sbachm@charite.de. Or to: David H. Ellison, Division of Nephrology and Hypertension (L334), Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA. Email: ellisond@ohsu.edu.

Authorship note: HD and JPBL contributed equally to this work. DHE and SB are equal corresponding authors.

Find articles by Smorodchenko, A. in: PubMed | Google Scholar

1Institute of Functional Anatomy and

2Department of Cell Biology and Neurobiology, Charité – Universitätsmedizin Berlin, Berlin, Germany.

3Department of Medical Biology, Faculty of Medicine, Ankara Yildirim Beyazit University, Ankara, Turkey.

4Division of Nephrology and Hypertension, School of Medicine, Oregon Health & Science University, Portland, Oregon, USA.

5Department of Human Medicine, MSB Medical School Berlin, Berlin, Germany.

6Division of Nephrology and Hypertension, Department of Medicine, Keck School of Medicine of University of Southern California, Los Angeles, California, USA.

7Department of Physiology, Xuzhou Medical University, Xuzhou, China.

8Department of Pharmacology, New York Medical College, Valhalla, New York, New York, USA.

9Department of Pediatric Respiratory Medicine and Department for Pediatric Radiology, Charité – Universitätsmedizin Berlin, Berlin, Germany.

10Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, Florida, USA.

11Department of Nephrology and Medical Intensive Care, Charité – Universitätsmedizin Berlin, Berlin, Germany.

12Institute of Physiology, Christian-Albrechts-University, Kiel, Germany.

13Department of Neurology, Jungers Center for Neurosciences Research, Oregon Health & Science University, Portland, Oregon, USA.

Address correspondence to: Sebastian Bachmann, Charité – Universitätsmedizin Berlin, Institut für Zell- und Neuroanatomie, Philippstr. 12, 10115 Berlin. Phone: 49.30.450.528.001; Email: sbachm@charite.de. Or to: David H. Ellison, Division of Nephrology and Hypertension (L334), Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA. Email: ellisond@ohsu.edu.

Authorship note: HD and JPBL contributed equally to this work. DHE and SB are equal corresponding authors.

Find articles by Su, X. in: PubMed | Google Scholar |

1Institute of Functional Anatomy and

2Department of Cell Biology and Neurobiology, Charité – Universitätsmedizin Berlin, Berlin, Germany.

3Department of Medical Biology, Faculty of Medicine, Ankara Yildirim Beyazit University, Ankara, Turkey.

4Division of Nephrology and Hypertension, School of Medicine, Oregon Health & Science University, Portland, Oregon, USA.

5Department of Human Medicine, MSB Medical School Berlin, Berlin, Germany.

6Division of Nephrology and Hypertension, Department of Medicine, Keck School of Medicine of University of Southern California, Los Angeles, California, USA.

7Department of Physiology, Xuzhou Medical University, Xuzhou, China.

8Department of Pharmacology, New York Medical College, Valhalla, New York, New York, USA.

9Department of Pediatric Respiratory Medicine and Department for Pediatric Radiology, Charité – Universitätsmedizin Berlin, Berlin, Germany.

10Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, Florida, USA.

11Department of Nephrology and Medical Intensive Care, Charité – Universitätsmedizin Berlin, Berlin, Germany.

12Institute of Physiology, Christian-Albrechts-University, Kiel, Germany.

13Department of Neurology, Jungers Center for Neurosciences Research, Oregon Health & Science University, Portland, Oregon, USA.

Address correspondence to: Sebastian Bachmann, Charité – Universitätsmedizin Berlin, Institut für Zell- und Neuroanatomie, Philippstr. 12, 10115 Berlin. Phone: 49.30.450.528.001; Email: sbachm@charite.de. Or to: David H. Ellison, Division of Nephrology and Hypertension (L334), Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA. Email: ellisond@ohsu.edu.

Authorship note: HD and JPBL contributed equally to this work. DHE and SB are equal corresponding authors.

Find articles by Nelson, J. in: PubMed | Google Scholar

1Institute of Functional Anatomy and

2Department of Cell Biology and Neurobiology, Charité – Universitätsmedizin Berlin, Berlin, Germany.

3Department of Medical Biology, Faculty of Medicine, Ankara Yildirim Beyazit University, Ankara, Turkey.

4Division of Nephrology and Hypertension, School of Medicine, Oregon Health & Science University, Portland, Oregon, USA.

5Department of Human Medicine, MSB Medical School Berlin, Berlin, Germany.

6Division of Nephrology and Hypertension, Department of Medicine, Keck School of Medicine of University of Southern California, Los Angeles, California, USA.

7Department of Physiology, Xuzhou Medical University, Xuzhou, China.

8Department of Pharmacology, New York Medical College, Valhalla, New York, New York, USA.

9Department of Pediatric Respiratory Medicine and Department for Pediatric Radiology, Charité – Universitätsmedizin Berlin, Berlin, Germany.

10Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, Florida, USA.

11Department of Nephrology and Medical Intensive Care, Charité – Universitätsmedizin Berlin, Berlin, Germany.

12Institute of Physiology, Christian-Albrechts-University, Kiel, Germany.

13Department of Neurology, Jungers Center for Neurosciences Research, Oregon Health & Science University, Portland, Oregon, USA.

Address correspondence to: Sebastian Bachmann, Charité – Universitätsmedizin Berlin, Institut für Zell- und Neuroanatomie, Philippstr. 12, 10115 Berlin. Phone: 49.30.450.528.001; Email: sbachm@charite.de. Or to: David H. Ellison, Division of Nephrology and Hypertension (L334), Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA. Email: ellisond@ohsu.edu.

Authorship note: HD and JPBL contributed equally to this work. DHE and SB are equal corresponding authors.

Find articles by Yang, C. in: PubMed | Google Scholar

1Institute of Functional Anatomy and

2Department of Cell Biology and Neurobiology, Charité – Universitätsmedizin Berlin, Berlin, Germany.

3Department of Medical Biology, Faculty of Medicine, Ankara Yildirim Beyazit University, Ankara, Turkey.

4Division of Nephrology and Hypertension, School of Medicine, Oregon Health & Science University, Portland, Oregon, USA.

5Department of Human Medicine, MSB Medical School Berlin, Berlin, Germany.

6Division of Nephrology and Hypertension, Department of Medicine, Keck School of Medicine of University of Southern California, Los Angeles, California, USA.

7Department of Physiology, Xuzhou Medical University, Xuzhou, China.

8Department of Pharmacology, New York Medical College, Valhalla, New York, New York, USA.

9Department of Pediatric Respiratory Medicine and Department for Pediatric Radiology, Charité – Universitätsmedizin Berlin, Berlin, Germany.

10Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, Florida, USA.

11Department of Nephrology and Medical Intensive Care, Charité – Universitätsmedizin Berlin, Berlin, Germany.

12Institute of Physiology, Christian-Albrechts-University, Kiel, Germany.

13Department of Neurology, Jungers Center for Neurosciences Research, Oregon Health & Science University, Portland, Oregon, USA.

Address correspondence to: Sebastian Bachmann, Charité – Universitätsmedizin Berlin, Institut für Zell- und Neuroanatomie, Philippstr. 12, 10115 Berlin. Phone: 49.30.450.528.001; Email: sbachm@charite.de. Or to: David H. Ellison, Division of Nephrology and Hypertension (L334), Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA. Email: ellisond@ohsu.edu.

Authorship note: HD and JPBL contributed equally to this work. DHE and SB are equal corresponding authors.

Find articles by Curry, J. in: PubMed | Google Scholar |

1Institute of Functional Anatomy and

2Department of Cell Biology and Neurobiology, Charité – Universitätsmedizin Berlin, Berlin, Germany.

3Department of Medical Biology, Faculty of Medicine, Ankara Yildirim Beyazit University, Ankara, Turkey.

4Division of Nephrology and Hypertension, School of Medicine, Oregon Health & Science University, Portland, Oregon, USA.

5Department of Human Medicine, MSB Medical School Berlin, Berlin, Germany.

6Division of Nephrology and Hypertension, Department of Medicine, Keck School of Medicine of University of Southern California, Los Angeles, California, USA.

7Department of Physiology, Xuzhou Medical University, Xuzhou, China.

8Department of Pharmacology, New York Medical College, Valhalla, New York, New York, USA.

9Department of Pediatric Respiratory Medicine and Department for Pediatric Radiology, Charité – Universitätsmedizin Berlin, Berlin, Germany.

10Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, Florida, USA.

11Department of Nephrology and Medical Intensive Care, Charité – Universitätsmedizin Berlin, Berlin, Germany.

12Institute of Physiology, Christian-Albrechts-University, Kiel, Germany.

13Department of Neurology, Jungers Center for Neurosciences Research, Oregon Health & Science University, Portland, Oregon, USA.

Address correspondence to: Sebastian Bachmann, Charité – Universitätsmedizin Berlin, Institut für Zell- und Neuroanatomie, Philippstr. 12, 10115 Berlin. Phone: 49.30.450.528.001; Email: sbachm@charite.de. Or to: David H. Ellison, Division of Nephrology and Hypertension (L334), Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA. Email: ellisond@ohsu.edu.

Authorship note: HD and JPBL contributed equally to this work. DHE and SB are equal corresponding authors.

Find articles by Duan, X. in: PubMed | Google Scholar |

1Institute of Functional Anatomy and

2Department of Cell Biology and Neurobiology, Charité – Universitätsmedizin Berlin, Berlin, Germany.

3Department of Medical Biology, Faculty of Medicine, Ankara Yildirim Beyazit University, Ankara, Turkey.

4Division of Nephrology and Hypertension, School of Medicine, Oregon Health & Science University, Portland, Oregon, USA.

5Department of Human Medicine, MSB Medical School Berlin, Berlin, Germany.

6Division of Nephrology and Hypertension, Department of Medicine, Keck School of Medicine of University of Southern California, Los Angeles, California, USA.

7Department of Physiology, Xuzhou Medical University, Xuzhou, China.

8Department of Pharmacology, New York Medical College, Valhalla, New York, New York, USA.

9Department of Pediatric Respiratory Medicine and Department for Pediatric Radiology, Charité – Universitätsmedizin Berlin, Berlin, Germany.

10Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, Florida, USA.

11Department of Nephrology and Medical Intensive Care, Charité – Universitätsmedizin Berlin, Berlin, Germany.

12Institute of Physiology, Christian-Albrechts-University, Kiel, Germany.

13Department of Neurology, Jungers Center for Neurosciences Research, Oregon Health & Science University, Portland, Oregon, USA.

Address correspondence to: Sebastian Bachmann, Charité – Universitätsmedizin Berlin, Institut für Zell- und Neuroanatomie, Philippstr. 12, 10115 Berlin. Phone: 49.30.450.528.001; Email: sbachm@charite.de. Or to: David H. Ellison, Division of Nephrology and Hypertension (L334), Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA. Email: ellisond@ohsu.edu.

Authorship note: HD and JPBL contributed equally to this work. DHE and SB are equal corresponding authors.

Find articles by Wang, W. in: PubMed | Google Scholar

1Institute of Functional Anatomy and

2Department of Cell Biology and Neurobiology, Charité – Universitätsmedizin Berlin, Berlin, Germany.

3Department of Medical Biology, Faculty of Medicine, Ankara Yildirim Beyazit University, Ankara, Turkey.

4Division of Nephrology and Hypertension, School of Medicine, Oregon Health & Science University, Portland, Oregon, USA.

5Department of Human Medicine, MSB Medical School Berlin, Berlin, Germany.

6Division of Nephrology and Hypertension, Department of Medicine, Keck School of Medicine of University of Southern California, Los Angeles, California, USA.

7Department of Physiology, Xuzhou Medical University, Xuzhou, China.

8Department of Pharmacology, New York Medical College, Valhalla, New York, New York, USA.

9Department of Pediatric Respiratory Medicine and Department for Pediatric Radiology, Charité – Universitätsmedizin Berlin, Berlin, Germany.

10Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, Florida, USA.

11Department of Nephrology and Medical Intensive Care, Charité – Universitätsmedizin Berlin, Berlin, Germany.

12Institute of Physiology, Christian-Albrechts-University, Kiel, Germany.

13Department of Neurology, Jungers Center for Neurosciences Research, Oregon Health & Science University, Portland, Oregon, USA.

Address correspondence to: Sebastian Bachmann, Charité – Universitätsmedizin Berlin, Institut für Zell- und Neuroanatomie, Philippstr. 12, 10115 Berlin. Phone: 49.30.450.528.001; Email: sbachm@charite.de. Or to: David H. Ellison, Division of Nephrology and Hypertension (L334), Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA. Email: ellisond@ohsu.edu.

Authorship note: HD and JPBL contributed equally to this work. DHE and SB are equal corresponding authors.

Find articles by Sharkovska, Y. in: PubMed | Google Scholar

1Institute of Functional Anatomy and

2Department of Cell Biology and Neurobiology, Charité – Universitätsmedizin Berlin, Berlin, Germany.

3Department of Medical Biology, Faculty of Medicine, Ankara Yildirim Beyazit University, Ankara, Turkey.

4Division of Nephrology and Hypertension, School of Medicine, Oregon Health & Science University, Portland, Oregon, USA.

5Department of Human Medicine, MSB Medical School Berlin, Berlin, Germany.

6Division of Nephrology and Hypertension, Department of Medicine, Keck School of Medicine of University of Southern California, Los Angeles, California, USA.

7Department of Physiology, Xuzhou Medical University, Xuzhou, China.

8Department of Pharmacology, New York Medical College, Valhalla, New York, New York, USA.

9Department of Pediatric Respiratory Medicine and Department for Pediatric Radiology, Charité – Universitätsmedizin Berlin, Berlin, Germany.

10Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, Florida, USA.

11Department of Nephrology and Medical Intensive Care, Charité – Universitätsmedizin Berlin, Berlin, Germany.

12Institute of Physiology, Christian-Albrechts-University, Kiel, Germany.

13Department of Neurology, Jungers Center for Neurosciences Research, Oregon Health & Science University, Portland, Oregon, USA.

Address correspondence to: Sebastian Bachmann, Charité – Universitätsmedizin Berlin, Institut für Zell- und Neuroanatomie, Philippstr. 12, 10115 Berlin. Phone: 49.30.450.528.001; Email: sbachm@charite.de. Or to: David H. Ellison, Division of Nephrology and Hypertension (L334), Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA. Email: ellisond@ohsu.edu.

Authorship note: HD and JPBL contributed equally to this work. DHE and SB are equal corresponding authors.

Find articles by Liu, R. in: PubMed | Google Scholar |

1Institute of Functional Anatomy and

2Department of Cell Biology and Neurobiology, Charité – Universitätsmedizin Berlin, Berlin, Germany.

3Department of Medical Biology, Faculty of Medicine, Ankara Yildirim Beyazit University, Ankara, Turkey.

4Division of Nephrology and Hypertension, School of Medicine, Oregon Health & Science University, Portland, Oregon, USA.

5Department of Human Medicine, MSB Medical School Berlin, Berlin, Germany.

6Division of Nephrology and Hypertension, Department of Medicine, Keck School of Medicine of University of Southern California, Los Angeles, California, USA.

7Department of Physiology, Xuzhou Medical University, Xuzhou, China.

8Department of Pharmacology, New York Medical College, Valhalla, New York, New York, USA.

9Department of Pediatric Respiratory Medicine and Department for Pediatric Radiology, Charité – Universitätsmedizin Berlin, Berlin, Germany.

10Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, Florida, USA.

11Department of Nephrology and Medical Intensive Care, Charité – Universitätsmedizin Berlin, Berlin, Germany.

12Institute of Physiology, Christian-Albrechts-University, Kiel, Germany.

13Department of Neurology, Jungers Center for Neurosciences Research, Oregon Health & Science University, Portland, Oregon, USA.

Address correspondence to: Sebastian Bachmann, Charité – Universitätsmedizin Berlin, Institut für Zell- und Neuroanatomie, Philippstr. 12, 10115 Berlin. Phone: 49.30.450.528.001; Email: sbachm@charite.de. Or to: David H. Ellison, Division of Nephrology and Hypertension (L334), Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA. Email: ellisond@ohsu.edu.

Authorship note: HD and JPBL contributed equally to this work. DHE and SB are equal corresponding authors.

Find articles by Yilmaz, D. in: PubMed | Google Scholar |

1Institute of Functional Anatomy and

2Department of Cell Biology and Neurobiology, Charité – Universitätsmedizin Berlin, Berlin, Germany.

3Department of Medical Biology, Faculty of Medicine, Ankara Yildirim Beyazit University, Ankara, Turkey.

4Division of Nephrology and Hypertension, School of Medicine, Oregon Health & Science University, Portland, Oregon, USA.

5Department of Human Medicine, MSB Medical School Berlin, Berlin, Germany.

6Division of Nephrology and Hypertension, Department of Medicine, Keck School of Medicine of University of Southern California, Los Angeles, California, USA.

7Department of Physiology, Xuzhou Medical University, Xuzhou, China.

8Department of Pharmacology, New York Medical College, Valhalla, New York, New York, USA.

9Department of Pediatric Respiratory Medicine and Department for Pediatric Radiology, Charité – Universitätsmedizin Berlin, Berlin, Germany.

10Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, Florida, USA.

11Department of Nephrology and Medical Intensive Care, Charité – Universitätsmedizin Berlin, Berlin, Germany.

12Institute of Physiology, Christian-Albrechts-University, Kiel, Germany.

13Department of Neurology, Jungers Center for Neurosciences Research, Oregon Health & Science University, Portland, Oregon, USA.

Address correspondence to: Sebastian Bachmann, Charité – Universitätsmedizin Berlin, Institut für Zell- und Neuroanatomie, Philippstr. 12, 10115 Berlin. Phone: 49.30.450.528.001; Email: sbachm@charite.de. Or to: David H. Ellison, Division of Nephrology and Hypertension (L334), Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA. Email: ellisond@ohsu.edu.

Authorship note: HD and JPBL contributed equally to this work. DHE and SB are equal corresponding authors.

Find articles by Quintanova, C. in: PubMed | Google Scholar

1Institute of Functional Anatomy and

2Department of Cell Biology and Neurobiology, Charité – Universitätsmedizin Berlin, Berlin, Germany.

3Department of Medical Biology, Faculty of Medicine, Ankara Yildirim Beyazit University, Ankara, Turkey.

4Division of Nephrology and Hypertension, School of Medicine, Oregon Health & Science University, Portland, Oregon, USA.

5Department of Human Medicine, MSB Medical School Berlin, Berlin, Germany.

6Division of Nephrology and Hypertension, Department of Medicine, Keck School of Medicine of University of Southern California, Los Angeles, California, USA.

7Department of Physiology, Xuzhou Medical University, Xuzhou, China.

8Department of Pharmacology, New York Medical College, Valhalla, New York, New York, USA.

9Department of Pediatric Respiratory Medicine and Department for Pediatric Radiology, Charité – Universitätsmedizin Berlin, Berlin, Germany.

10Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, Florida, USA.

11Department of Nephrology and Medical Intensive Care, Charité – Universitätsmedizin Berlin, Berlin, Germany.

12Institute of Physiology, Christian-Albrechts-University, Kiel, Germany.

13Department of Neurology, Jungers Center for Neurosciences Research, Oregon Health & Science University, Portland, Oregon, USA.

Address correspondence to: Sebastian Bachmann, Charité – Universitätsmedizin Berlin, Institut für Zell- und Neuroanatomie, Philippstr. 12, 10115 Berlin. Phone: 49.30.450.528.001; Email: sbachm@charite.de. Or to: David H. Ellison, Division of Nephrology and Hypertension (L334), Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA. Email: ellisond@ohsu.edu.

Authorship note: HD and JPBL contributed equally to this work. DHE and SB are equal corresponding authors.

Find articles by Emberley, K. in: PubMed | Google Scholar

1Institute of Functional Anatomy and

2Department of Cell Biology and Neurobiology, Charité – Universitätsmedizin Berlin, Berlin, Germany.

3Department of Medical Biology, Faculty of Medicine, Ankara Yildirim Beyazit University, Ankara, Turkey.

4Division of Nephrology and Hypertension, School of Medicine, Oregon Health & Science University, Portland, Oregon, USA.

5Department of Human Medicine, MSB Medical School Berlin, Berlin, Germany.

6Division of Nephrology and Hypertension, Department of Medicine, Keck School of Medicine of University of Southern California, Los Angeles, California, USA.

7Department of Physiology, Xuzhou Medical University, Xuzhou, China.

8Department of Pharmacology, New York Medical College, Valhalla, New York, New York, USA.

9Department of Pediatric Respiratory Medicine and Department for Pediatric Radiology, Charité – Universitätsmedizin Berlin, Berlin, Germany.

10Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, Florida, USA.

11Department of Nephrology and Medical Intensive Care, Charité – Universitätsmedizin Berlin, Berlin, Germany.

12Institute of Physiology, Christian-Albrechts-University, Kiel, Germany.

13Department of Neurology, Jungers Center for Neurosciences Research, Oregon Health & Science University, Portland, Oregon, USA.

Address correspondence to: Sebastian Bachmann, Charité – Universitätsmedizin Berlin, Institut für Zell- und Neuroanatomie, Philippstr. 12, 10115 Berlin. Phone: 49.30.450.528.001; Email: sbachm@charite.de. Or to: David H. Ellison, Division of Nephrology and Hypertension (L334), Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA. Email: ellisond@ohsu.edu.

Authorship note: HD and JPBL contributed equally to this work. DHE and SB are equal corresponding authors.

Find articles by Emery, B. in: PubMed | Google Scholar |

1Institute of Functional Anatomy and

2Department of Cell Biology and Neurobiology, Charité – Universitätsmedizin Berlin, Berlin, Germany.

3Department of Medical Biology, Faculty of Medicine, Ankara Yildirim Beyazit University, Ankara, Turkey.

4Division of Nephrology and Hypertension, School of Medicine, Oregon Health & Science University, Portland, Oregon, USA.

5Department of Human Medicine, MSB Medical School Berlin, Berlin, Germany.

6Division of Nephrology and Hypertension, Department of Medicine, Keck School of Medicine of University of Southern California, Los Angeles, California, USA.

7Department of Physiology, Xuzhou Medical University, Xuzhou, China.

8Department of Pharmacology, New York Medical College, Valhalla, New York, New York, USA.

9Department of Pediatric Respiratory Medicine and Department for Pediatric Radiology, Charité – Universitätsmedizin Berlin, Berlin, Germany.

10Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, Florida, USA.

11Department of Nephrology and Medical Intensive Care, Charité – Universitätsmedizin Berlin, Berlin, Germany.

12Institute of Physiology, Christian-Albrechts-University, Kiel, Germany.

13Department of Neurology, Jungers Center for Neurosciences Research, Oregon Health & Science University, Portland, Oregon, USA.

Address correspondence to: Sebastian Bachmann, Charité – Universitätsmedizin Berlin, Institut für Zell- und Neuroanatomie, Philippstr. 12, 10115 Berlin. Phone: 49.30.450.528.001; Email: sbachm@charite.de. Or to: David H. Ellison, Division of Nephrology and Hypertension (L334), Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA. Email: ellisond@ohsu.edu.

Authorship note: HD and JPBL contributed equally to this work. DHE and SB are equal corresponding authors.

Find articles by Himmerkus, N. in: PubMed | Google Scholar

1Institute of Functional Anatomy and

2Department of Cell Biology and Neurobiology, Charité – Universitätsmedizin Berlin, Berlin, Germany.

3Department of Medical Biology, Faculty of Medicine, Ankara Yildirim Beyazit University, Ankara, Turkey.

4Division of Nephrology and Hypertension, School of Medicine, Oregon Health & Science University, Portland, Oregon, USA.

5Department of Human Medicine, MSB Medical School Berlin, Berlin, Germany.

6Division of Nephrology and Hypertension, Department of Medicine, Keck School of Medicine of University of Southern California, Los Angeles, California, USA.

7Department of Physiology, Xuzhou Medical University, Xuzhou, China.

8Department of Pharmacology, New York Medical College, Valhalla, New York, New York, USA.

9Department of Pediatric Respiratory Medicine and Department for Pediatric Radiology, Charité – Universitätsmedizin Berlin, Berlin, Germany.

10Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, Florida, USA.

11Department of Nephrology and Medical Intensive Care, Charité – Universitätsmedizin Berlin, Berlin, Germany.

12Institute of Physiology, Christian-Albrechts-University, Kiel, Germany.

13Department of Neurology, Jungers Center for Neurosciences Research, Oregon Health & Science University, Portland, Oregon, USA.

Address correspondence to: Sebastian Bachmann, Charité – Universitätsmedizin Berlin, Institut für Zell- und Neuroanatomie, Philippstr. 12, 10115 Berlin. Phone: 49.30.450.528.001; Email: sbachm@charite.de. Or to: David H. Ellison, Division of Nephrology and Hypertension (L334), Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA. Email: ellisond@ohsu.edu.

Authorship note: HD and JPBL contributed equally to this work. DHE and SB are equal corresponding authors.

Find articles by Bleich, M. in: PubMed | Google Scholar |

1Institute of Functional Anatomy and

2Department of Cell Biology and Neurobiology, Charité – Universitätsmedizin Berlin, Berlin, Germany.

3Department of Medical Biology, Faculty of Medicine, Ankara Yildirim Beyazit University, Ankara, Turkey.

4Division of Nephrology and Hypertension, School of Medicine, Oregon Health & Science University, Portland, Oregon, USA.

5Department of Human Medicine, MSB Medical School Berlin, Berlin, Germany.

6Division of Nephrology and Hypertension, Department of Medicine, Keck School of Medicine of University of Southern California, Los Angeles, California, USA.

7Department of Physiology, Xuzhou Medical University, Xuzhou, China.

8Department of Pharmacology, New York Medical College, Valhalla, New York, New York, USA.

9Department of Pediatric Respiratory Medicine and Department for Pediatric Radiology, Charité – Universitätsmedizin Berlin, Berlin, Germany.

10Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, Florida, USA.

11Department of Nephrology and Medical Intensive Care, Charité – Universitätsmedizin Berlin, Berlin, Germany.

12Institute of Physiology, Christian-Albrechts-University, Kiel, Germany.

13Department of Neurology, Jungers Center for Neurosciences Research, Oregon Health & Science University, Portland, Oregon, USA.

Address correspondence to: Sebastian Bachmann, Charité – Universitätsmedizin Berlin, Institut für Zell- und Neuroanatomie, Philippstr. 12, 10115 Berlin. Phone: 49.30.450.528.001; Email: sbachm@charite.de. Or to: David H. Ellison, Division of Nephrology and Hypertension (L334), Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA. Email: ellisond@ohsu.edu.

Authorship note: HD and JPBL contributed equally to this work. DHE and SB are equal corresponding authors.

Find articles by Ellison, D. in: PubMed | Google Scholar

1Institute of Functional Anatomy and

2Department of Cell Biology and Neurobiology, Charité – Universitätsmedizin Berlin, Berlin, Germany.

3Department of Medical Biology, Faculty of Medicine, Ankara Yildirim Beyazit University, Ankara, Turkey.

4Division of Nephrology and Hypertension, School of Medicine, Oregon Health & Science University, Portland, Oregon, USA.

5Department of Human Medicine, MSB Medical School Berlin, Berlin, Germany.

6Division of Nephrology and Hypertension, Department of Medicine, Keck School of Medicine of University of Southern California, Los Angeles, California, USA.

7Department of Physiology, Xuzhou Medical University, Xuzhou, China.

8Department of Pharmacology, New York Medical College, Valhalla, New York, New York, USA.

9Department of Pediatric Respiratory Medicine and Department for Pediatric Radiology, Charité – Universitätsmedizin Berlin, Berlin, Germany.

10Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, Florida, USA.

11Department of Nephrology and Medical Intensive Care, Charité – Universitätsmedizin Berlin, Berlin, Germany.

12Institute of Physiology, Christian-Albrechts-University, Kiel, Germany.

13Department of Neurology, Jungers Center for Neurosciences Research, Oregon Health & Science University, Portland, Oregon, USA.

Address correspondence to: Sebastian Bachmann, Charité – Universitätsmedizin Berlin, Institut für Zell- und Neuroanatomie, Philippstr. 12, 10115 Berlin. Phone: 49.30.450.528.001; Email: sbachm@charite.de. Or to: David H. Ellison, Division of Nephrology and Hypertension (L334), Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA. Email: ellisond@ohsu.edu.

Authorship note: HD and JPBL contributed equally to this work. DHE and SB are equal corresponding authors.

Find articles by Bachmann, S. in: PubMed | Google Scholar

Authorship note: HD and JPBL contributed equally to this work. DHE and SB are equal corresponding authors.

Published June 5, 2025 - More info

Published in Volume 10, Issue 13 on July 8, 2025
JCI Insight. 2025;10(13):e190992. https://doi.org/10.1172/jci.insight.190992.
© 2025 Demirci et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. Published June 5, 2025 - Version history
Received: January 15, 2025; Accepted: May 28, 2025 View PDF Related video: Pathways for monovalent and divalent cation transport and distinct cell types

In this episode, David Ellison, Sebastian Bachman, and Jessica Bahena-Lopez describe how their results show that there are three cell types along the kidney thick ascending limb, enabling it to adjust solute absorption selectively to maintain homeostasis.

Abstract

Kidney thick ascending limb (TAL) cells reabsorb sodium, potassium, calcium, and magnesium and contribute to urinary concentration. These cells are typically viewed as a single type that recycles potassium across the apical membrane and generates a lumen-positive transepithelial voltage driving calcium and magnesium reabsorption, though variability in potassium channel expression has been reported. Additionally, recent transcriptomic analyses suggest that different cell types exist along this segment, but classifications have varied and have not led to a new consensus model. We used immunolocalization, electrophysiology, and enriched single-nucleus RNA-Seq to identify TAL cell types in rats, mice, and humans. We identified 3 major TAL cell types defined by expression of potassium channels and claudins. One has apical potassium channels, has low basolateral potassium conductance, and is bordered by a monovalent cation-permeable claudin. A second lacks apical potassium channels, has high basolateral potassium conductance, and is bordered by calcium- and magnesium-permeable claudins. A third type also lacks apical potassium channels and has high basolateral potassium conductance, but these cells are ringed by monovalent cation-permeable claudins. The recognition of diverse cell types may resolve longstanding questions about how solute transport can be modulated selectively and how disruption of these cells leads to human disease.

Graphical Abstract Introduction

The kidney thick ascending limb (TAL) reabsorbs several filtered solutes and contributes importantly to urinary concentration and dilution. As physiological challenges to extracellular fluid volume, divalent ion metabolism, or water balance may occur independently, the TAL must b