Gentamicin Inhibits Ca2+ Channel TRPV5 and Induces Calciuresis Independent of the Calcium-Sensing Receptor–Claudin-14 Pathway
Abstract
The antibiotic gentamicin, frequently used to treat Gram-negative bacteria infections, has significant side effects, including renal Ca2+ wasting. Gentamicin has been presumed to induce calciuresis by activating the renal Ca2+-sensing receptor, which would increase expression of the pore-blocking protein claudin-14 and reduce Ca2+ reabsorption in the thick ascending limb. However, this hypothesis has not been confirmed experimentally. Using a combination of mouse models with impaired Ca2+ reabsorption in the proximal tubule and the thick ascending limb, we show that neither acute nor chronic gentamicin administration induces calciuresis by acting on these segments. Instead, gentamicin blocks activity of the distal nephron Ca2+ channel transient receptor potential vanilloid 5 (TRPV5) and decreases calciotropic protein expression, thereby reducing distal nephron Ca2+ reabsorption. These findings illuminate the mechanism underlying gentamicin-induced urinary Ca2+ loss.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Mar 01, 2022
- Source ID
- 10.1681/asn.2021030392
Entities
People
- Henrik Dimke
- Justin J. Lee
- Matthias T. Wolf
- Megan R. Beggs
- Patrícia Ferreira
- R Todd Alexander
- Sung-wan An
- Wouter H. Van Megen
Organizations
- Canadian Institutes of Health Research
- Independent Research Fund Denmark
- National Institutes of Health
- Odense University Hospital
- United States Department of Defense
- University of Alberta
- University of Texas at Austin