Up-regulation of megakaryocytic Na(+)/Ca(2+) exchange in klotho-deficient mice

Biochemical and Biophysical Research Communications
Evi SchmidFlorian Lang

Abstract

The active form of vitamin D, 1,25(OH)₂D₃, is a powerful regulator of cytosolic Ca(2+)-concentration ([Ca(2+)]i) in a variety of cell types. The formation of 1,25(OH)₂D₃ is inhibited by FGF23, an effect requiring presence of klotho. 1,25(OH)₂D₃ plasma levels are excessive in klotho-deficient mice (kl/kl). A previous study revealed that klotho-deficiency is followed by decreased activation of platelets, an effect at least in part due to blunted store operated Ca(2+) entry (SOCE). In other cell types 1,25(OH)₂D₃ has been shown to up-regulate the Na(+)/Ca(2+)-exchanger, which could, depending on cell membrane potential and cytosolic Na(+) concentration, either decrease or increase [Ca(2+)]i. The present study explored whether Na(+)/Ca(2+)-exchanger activity is different in megakaryocytes isolated from kl/kl mice than in megakaryocytes isolated from wild type mice. Na(+)/Ca(2+)-exchanger induced currents were determined by whole cell patch clamp and the Na(+)/Ca(2+)-exchanger induced alterations of [Ca(2+)]i by Fura-2 fluorescence. As a result, the inward current and the increase of [Ca(2+)]i following replacement of extracellular Na(+) by NMDG were higher in kl/kl megakaryocytes than in wild type megakaryocytes, a difference abrog...Continue Reading

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