Relationship between total and free cellular Mg(2+) during metabolic stimulation of rat cardiac myocytes and perfused hearts.

The changes in total Mg were compared with changes in cytosolic free Mg(2+) 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 Mg(2+) measured with fluorescent indicator are small and result in changes of cytosolic free Mg(2+) equivalent to 90-140 microM. In perfused hearts, beta-adrenergic stimulation results in a loss of total Mg larger than 0.5 micromol per gram of heart corresponding to 9% loss of total Mg content of the heart (estimated to be 5.8 micromol). Under these conditions there is no change in cytosolic free Mg(2+) or the major buffer of cytosolic Mg(2+), ATP, as measured by (31)P 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 Mg(2+) relatively unchanged during the observed cellular massive translocation of total Mg. Hence, Mg(2+) may regulate metabolic functions not within the cytosol but in locations where its concentration oscillates, such as extracellular fluid and intracellular compartments.