Membrane localization, Caveolin-3 association and rapid actions of vitamin D receptor in cardiac myocytes

• Published in: Steroids Vol. 75; no. 8; pp. 555 - 559
• Main Authors: Zhao, Guisheng, Simpson, Robert U.
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Kidlington Elsevier Inc 01.08.2010; Elsevier
• Subjects: Animals; Biological and medical sciences; Cardiac contractility; Cardiomyocytes; Caveolin 3 - metabolism; Caveolin-3; Cell Membrane - drug effects; Cell Membrane - metabolism; Fundamental and applied biological sciences. Psychology; Male; Microtubules - drug effects; Microtubules - metabolism; Microtubules - ultrastructure; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - metabolism; Myocytes, Cardiac - ultrastructure; Rats; Rats, Sprague-Dawley; Receptors, Calcitriol - metabolism; Sarcolemma - drug effects; Sarcolemma - metabolism; Sarcolemma - ultrastructure; Structure-Activity Relationship; Vertebrates: endocrinology; Vitamin D; Vitamin D - analogs & derivatives; Vitamin D - pharmacology; Vitamin D receptor; Cardiomyocytes; Vitamin D; Cardiac contractility; Vitamin D receptor; Caveolin-3; Heart; Micronutrient; Contractility; Circulatory system; Localization; Heart cell; Myocyte
• ISSN: 0039-128X; 1878-5867
• DOI: 10.1016/j.steroids.2009.12.001

The active form of vitamin D, 1alpha, 25-dihydroxyvitamin D 3 (1,25(OH) 2D 3), mediates both genomic and rapid non-genomic actions in heart cells. We have previously shown that the vitamin D receptor (VDR) is located in the t-tubular structure of cardiomyocytes. Here we show that VDR specifically interacts with Caveolin-3 in the t-tubules and sarcolemma of adult rat cardiac myocytes. Co-immunoprecipitation studies using VDR antibodies revealed that Caveolin-3 specifically co-precipitates with the VDR and similarly the VDR is co-precipitated with Caveolin-3 antibody. Confocal immuno-fluorescence microscopy analysis also showed co-localization of VDR and Caveolin-3 in t-tubules and sarcolemma. The non-genomic effects of the functional VDR were studied in electrically stimulated myocytes isolated from adult rat hearts. Sarcomere shortening and re-lengthening were measured in 1,25(OH) 2D 3 treated cardiac myocytes. A 1 nM treatment decreased peak shortening within minutes, suggesting a rapid effect through the membrane-bound VDR. This novel finding of the interaction between VDR and Caveolin-3 is fundamentally important in understanding 1,25(OH) 2D 3 signal transduction in heart cells and provides further evidence that VDR plays a role in regulation of heart structure and function.