Mysteries of Magnesium Homeostasis
This article requires a subscription to view the full text. If you have a subscription you may use the login form below to view the article. Access to this article can also be purchased.
In this issue of Circulation Research, Romani and colleagues1 report that insulin stimulates uptake of ionized magnesium (Mg2+) into heart. This study is the latest in a series by Romani, Scarpa, and colleagues regarding hormone-regulated Mg2+ 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 (Ca2+) is regulated and how it regulates cell function. However, the more abundant divalent cation Mg2+ still holds many secrets for us to unravel. Ca2+ signaling is facilitated by the large Ca2+ gradients (up to 10 000-fold) across the plasma and sarcoplasmic reticulum (SR) membranes. In contrast, only small gradients of Mg2+ (generally a factor of 2 or less) are reported across the plasma or intracellular membranes.3 4 5 In contrast to Ca2+ signaling, agonists do not cause large (order of magnitude) alterations in cytosolic Mg2+. 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 Mg2+. This lack of change in cytosolic Mg2+ has led many investigators to question whether Mg2+ is involved in hormone signaling.
Is Intracellular Mg2+ Stable or Does It Function as an Intracellular Messenger?
Cytosolic Mg2+, which is regulated by plasma membrane and organelle transport, and by intracellular binding, is maintained far from electrochemical equilibrium. If cytosolic Mg2+ were at electrochemical equilibrium, it would be ≈188 mmol/L, assuming a membrane potential of −70 mV and extracellular Mg2+ of 1 mmol/L. Because the plasma membrane is not impermeable to Mg2+, there must be transport mechanisms to extrude Mg2+ against its electrochemical gradient (for reviews, see References 6 7 8 ). However, …