Related Experiment Video
Updated: Jun 20, 2026
Calcium Imaging in Mouse Superior Colliculus
Published on: April 21, 2023
Impaired renal calcium absorption in mice lacking calcium channel beta 3 subunits
José F Bernardo1, Clara E Magyar, W Bruce Sneddon
1Department of Medicine, Renal Electrolyte Division, W1340 Biomedical Science Tower, Pittsburgh, PA 15261, USA.
Abstract:
Transgenic mice lacking calcium channel beta3 subunits (CaVbeta3) were used to determine the involvement of a multimeric calcium channel in mediating stimulated renal calcium absorption. We measured the ability of calcium channel beta3 subunit-null (CaVbeta3-/-) and wild-type (CaVbeta3+/+) mice to increase renal calcium absorption in response to the calcium-sparing diuretic chlorothiazide (CTZ). Control rates of fractional sodium excretion were comparable in CaVbeta3-/- and CaVbeta3+/+ mice and CTZ increased sodium excretion similarly in both groups. CTZ enhanced calcium absorption only in wild-type CaVbeta3+/+ mice. This effect was specific for diuretics acting on distal tubules because both CaVbeta3-/- and CaVbeta3+/+ mice responded comparably to furosemide. The absence of beta3 subunits resulted in compensatory increases of TrpV5 calcium channels, the plasma membrane Ca-ATPase, NCX1 Na/Ca exchanger protein, and calbindin-D9k but not calbindin-D28k. We conclude that TrpV5 mediates basal renal calcium absorption and that a multimeric calcium channel that includes CaVbeta3 mediates stimulated calcium transport.
Insights
Mice lacking calcium channel beta3 subunits show impaired stimulated renal calcium absorption. This suggests a multimeric calcium channel, including beta3 subunits, is crucial for this process.
Area of Science:
- Nephrology
- Molecular Biology
- Physiology
Background:
- Renal calcium absorption is vital for calcium homeostasis.
- The role of specific calcium channel subunits in stimulated renal calcium transport remains incompletely understood.
Purpose of the Study:
- To investigate the involvement of the calcium channel beta3 subunit (CaVbeta3) in mediating stimulated renal calcium absorption.
- To determine the functional significance of CaVbeta3 in the context of diuretic-induced calcium handling.
Main Methods:
- Utilized transgenic mice lacking the CaVbeta3 subunit (CaVbeta3-/-) and wild-type littermates (CaVbeta3+/+).
- Measured renal calcium absorption and fractional sodium excretion in response to chlorothiazide (CTZ) and furosemide.
- Assessed the expression levels of key calcium transport proteins, including TrpV5, Ca-ATPase, NCX1, and calbindins.
Main Results:
- Chlorothiazide (CTZ) stimulated renal calcium absorption exclusively in wild-type mice, not in CaVbeta3-/- mice.
- The diuretic response to furosemide was similar in both genotypes, indicating a distal tubule-specific effect of CTZ.
- Absence of CaVbeta3 led to compensatory upregulation of TrpV5, Ca-ATPase, NCX1, and calbindin-D9k, but not calbindin-D28k.
Conclusions:
- TrpV5 channels are essential for basal renal calcium absorption.
- A multimeric calcium channel complex incorporating the CaVbeta3 subunit is critical for mediating stimulated renal calcium absorption, particularly in response to distal tubule diuretics like CTZ.
