Mysteries of Magnesium Homeostasis

n this issue of Circulation Research, Romani and colleagues 1 report that insulin stimulates uptake of ionized magnesium (Mg 2ϩ ) into heart.This study is the latest in a series by Romani, Scarpa, and colleagues regarding hormoneregulated Mg 2ϩ fluxes in heart and liver (References 1 and 2 and references therein).Over the past several decades, we have begun to uncover the mysteries of how cytosolic ionized calcium (Ca 2ϩ ) is regulated and how it regulates cell function.However, the more abundant divalent cation Mg 2ϩ still holds many secrets for us to unravel.Ca 2ϩ signaling is facilitated by the large Ca 2ϩ gradients (up to 10 000-fold) across the plasma and sarcoplasmic reticulum (SR) membranes.]5 In contrast to Ca 2ϩ signaling, agonists do not cause large (order of magnitude) alterations in cytosolic Mg 2ϩ .Even upon hormonal stimulation, of heart and liver, which results in a 10% to 15% change in total cell magnesium, there is little or no change in cytosolic Mg 2ϩ .This lack of change in cytosolic Mg 2ϩ has led many investigators to question whether Mg 2ϩ is involved in hormone signaling.