Send to:

Choose Destination
See comment in PubMed Commons below
Endocrinology. 2008 Feb;149(2):558-64. Epub 2007 Nov 1.

Functional vitamin D receptor (VDR) in the t-tubules of cardiac myocytes: VDR knockout cardiomyocyte contractility.

Author information

  • 1Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.


We have previously shown that the active form of vitamin D, 1,25 dihydroxyvitamin D3 [1,25(OH)(2)D(3)], has both genomic and rapid nongenomic effects in heart cells; however, the subcellular localization of the vitamin D receptor (VDR) in heart has not been studied. Here we show that in adult rat cardiac myocytes the VDR is primarily localized to the t-tubule. Using immunofluorescence and Western blot analysis, we show that the VDR is closely associated with known t-tubule proteins. Radioligand binding assays using (3)H-labeled 1,25(OH)(2)D(3) demonstrate that a t-tubule membrane fraction isolated from homogenized rat ventricles contains a 1,25(OH)(2)D(3)-binding activity similar to the classic VDR. For the first time, we show that cardiac myocytes isolated from VDR knockout mice show accelerated rates of contraction and relaxation as compared with wild type and that 1,25(OH)(2)D(3) directly affects contractility in the wild-type but not the knockout cardiac myocyte. Moreover, we observed that acute (5 min) exposure to 1,25(OH)(2)D(3) altered the rate of relaxation. A receptor localized to t-tubules in the heart is ideally positioned to exert an immediate effect on signal transduction mediators and ion channels. This novel discovery is fundamentally important in understanding 1,25(OH)(2)D(3) signal transduction in heart cells and provides further evidence that the VDR plays a role in heart structure and function.

[PubMed - indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Atypon Icon for PubMed Central
    Loading ...
    Write to the Help Desk