Relationship between Total and Free Cellular Mg2+ during Metabolic Stimulation of Rat Cardiac Myocytes and Perfused Hearts

The changes in total Mg were compared with changes in cytosolic free Mg2+ during metabolic stimulation of collagenase-dispersed rat cardiac myocytes or Langendorff-perfused rat hearts. In myocytes the addition of agents leading to cAMP increase or protein kinase C activation results in a loss or gain of more than 5% of total Mg content within 3 min (i.e., 3–4 nmol Mg/mg protein). Under the same conditions, changes in cytosolic free Mg2+ measured with fluorescent indicator are small and result in changes of cytosolic free Mg2+ equivalent to 90–140 μM. In perfused hearts, β-adrenergic stimulation results in a loss of total Mg larger than 0.5 μmol per gram of heart corresponding to 9% loss of total Mg content of the heart (estimated to be 5.8 μmol). Under these conditions there is no change in cytosolic free Mg2+ or the major buffer of cytosolic Mg2+, ATP, as measured by 31P NMR. These data suggest that a major redistribution of total Mg occurs in intracellular organelles or in cytosolic buffers in order to maintain cytosolic free Mg2+ relatively unchanged during the observed cellular massive translocation of total Mg. Hence, Mg2+ may regulate metabolic functions not within the cytosol but in locations where its concentration oscillates, such as extracellular fluid and intracellular compartments.