The ionic control of 1,25-dihydroxyvitamin D-3 synthesis in isolated chick renal mitochondria. The role of potassium.

In previous studies it was found that change in the concentrations of Ca2+, H+, and HPO2-4 in the incubation medium altered the rates of synthesis of 1,25-dihydroxyvitamin D-3 (1,25(OH)2D-3) by isolated renal mitochondria obtained from D-deficient chicks. The present studies demonstrate that raising the medium concentration of K+ from 1 to 50 mM leads to a 6-fold increase in rate of 1,25(OH)2D-3 synthesis by isolated chick mitochondria; that the magnitnitude of this K+-dependent stimulation is enhaced by optimal concentrations of calcium (pCa = 5) and phosphate (pPi = 3) (3 mM) but not by pH (from 6.8 to 7.4); that the effect is not produced by similar changes in media Na+ concentration; and that the stimulatory effect of K+ is not blocked by ruthenium red, and inhibitor of calcium transport and of the calcium-dependent stimulation of mitochondrial 1,25(OH) 2D-3 synthesis. It was also found that valinomycin, a K+-specific ionophore, enhanced the sensitivity of the mitochondrial 1 alpha-hydroxylase activity to K+. In the presence of valinomycin, an increase of pK+ to 3 was sufficient to cause a significant stimulation of 1,25(OH)2D-3 synthesis. It was concluded that changes in the ion content of the mitochondrial matrix space regulated the activity of the 1 alpha-hydroxylase.