RAPID STIMULATION OF CALCIUM-UPTAKE AND PROTEIN-PHOSPHORYLATION IN ISOLATED CARDIAC-MUSCLE BY 1,25-DIHYDROXYVITAMIN D3

1,25-Dihydroxyvitamin D3 has been shown to induce rapid changes in calcium fluxes in skeletal muscle and other target tissues independently of gene activation. The possibility that the hormone would produce similar effects in heart where 1,25-dihydroxyvitamin D3 receptors and activities have been shown, was studied. A significant increase of Ca-45 uptake by left ventricular slices from vitamin D-deficient chicks was observed upon incubation for 1-10 min with physiological doses of 1,25-dihydroxyvitamin D3. This stimulation was dose-dependent and specific for the hormone when compared with vitamin D3, 25-hydroxyvitamin D3 and 24,25-dihydroxyvitamin D3 and could not be associated to changes in lipid synthesis as assessed by measurements of [H-3]glycerol incorporation into cardiac tissue lipids. The Ca channel blockers nifedipine (30-mu-M) and verapamil (10-mu-M) abolished the increase in Ca uptake produced by 1,25-dihydroxyvitamin D3. The rapid effects of the hormone on heart Ca influx were accompanied by a stimulation of the phosphorylation of two microsomal proteins of 43 kDa and 55 kDa. These results further support a direct action of 1,25-dihydroxyvitamin D3 in the regulation of cardiac muscle Ca metabolism which may involve activation of Ca channels.