Rapid changes in skeletal muscle calcium uptake induced in vitro by 1,25-dihydroxyvitamin D3 are suppressed by calcium channel blockers.
Previous investigations have shown that 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] stimulates muscle Ca uptake through a nuclear mechanism. The possibility that 1,25-(OH)2D3 would induce rapid changes in muscle Ca fluxes independent of de novo protein synthesis was investigated in the present work. In vitro preparations of soleus muscles obtained from vitamin D-deficient chicks were used. A significant increase in 45Ca labeling of the tissue was already observed after 3-min treatment with 2.4 X 10(-10) M 1,25-(OH)2D3. This early stimulation in muscle Ca uptake became maximal at 10-15 min. Cycloheximide (50 microM) did not block the effect of the metabolite at 15 and 30 min. However, the antibiotic effectively blocked the increase in Ca uptake induced by 1,25-(OH)2D3 after 1-h treatment. The rapid 1,25-(OH)2D3-dependent stimulation of 45Ca labeling of soleus muscle was not associated to changes in lipid synthesis as assessed by measurements of 3H-glycerol incorporation into the tissue lipids. However, the calcium antagonists verapamil and nifedipine (50 microM) abolished the stimulation in Ca uptake produced by 1,25-(OH)2D3 in 5 min. These results suggest that 1,25-(OH)2D3 can act directly at the muscle membrane level affecting Ca fluxes through Ca channels.
D000818:Animals; D002117:Calcitriol / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002132:Calcium Radioisotopes; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002645:Chickens; D003513:Cycloheximide / Q000494:pharmacology; D005990:Glycerol / Q000378:metabolism; D007473:Ion Channels / Q000378:metabolism; D007700:Kinetics; D050356:Lipid Metabolism; D009132:Muscles / Q000187:drug effects / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology; D014808:Vitamin D Deficiency / Q000378:metabolism
D002121:Calcium Channel Blockers; D002132:Calcium Radioisotopes; D007473:Ion Channels; D003513:Cycloheximide; D014700:Verapamil; D002117:Calcitriol; D009543:Nifedipine; D005990:Glycerol; D002118:Calcium