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Since intracellular free Mg^(2+) ([Mg^(2+)]_i) appears to be tightly regulated following cellular energy depletion, we hypothesized that the increase in [Mg^(2+)]_i would result in Mg^(2+) extrusion into circulation. Extracellualr Mg^(2+) contents ([Mg^(2+)]_o) were measured in rat erythrocytes, the perfused heart and liver, and plasma in the anesthetized rat. Animals were injected intraperitoneally with sodium nitrite (NaNO₂) and plasma Mg2+ was measured after the injection and then 10 and 20 minutes later. An increase in circulating (plasma) Mg^(2+) ([Mg^(2+)]-c) and methemoglobin was observed in animals injected with NaNO₂ (30 ㎎/Kg). The time course of the effects demonstrated that [Mg^(2+)]_c and methemoglobin continued to increase 10 minutes after the NaNO₂ injection. Under these conditions, there was a sustained increase in [Mg^(2+)]-c, but not in methemoglobin, which was inhibited by pretreatment with potassium cyanide (KCN, 4 ㎎/Kg), indicating that an increase in [Mg^(2+)]-c was accompanied by ATP depletion. Injection of rotenone (0.9 ㎎/Kg) or 2,4-dinitrophenol (15㎎/Kg) also induced an increase in [Mg^(2+)]-c. Reduced respiration rate from 100/min to 10/min during 30 minutes also caused a time-dependent rise in [Mg^(2+)]-c. These increase in [Mg^(2+)]-c were inhibited by pretreatment with KCN. In addition, ATP depletion by NaNO₂ or KCN sustainedly increased the [Mg^(2+)]_o in rat erythrocytes. Mg^(2+) efflux was stimulated by KCN in the perfused heart and liver, but not by NaNO₂. These results suggest that the activation of Mg^(2+) effluxes into the circulation is directly dependent on the ATP depletion-induced increase in [Mg^(2+)]_i and heart, liver and erythrocytes have a major pool of Mg^(2+) that can be mobilized upon cellular energy state.
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