Myocardial loss of functional magnesium. I. Effect on mitochondrial integrity and potassium retention.

There is growing interest in the importance of magnesium in myocardial structure and function. Most clinicians in the United States still place greatest emphasis on potassium loss in the e tiology or intensification of cardiomyopathy . This paper presents an analysis of the data that indicate that the magnesium loss from the heart , as from other tissues, interferes with the cellular machinery without which cardiac potassium cannot be maintained. Thus, magnesium loss predisposes to potassium loss. The cardiac loss of potassium seen in magnesium deficiency was first attributed by Vitale and his associates ( 14 , 57) to the necessity of magnesium for the normal functioning and structural integrity of heart mitochondria. They correlated the decreased oxidat ive activity and/or uncoupling of oxidative phosphorylation by cardiac mitochondria from thei r magnesium-deficient animals ( 14, 55 , 58) with the biochemically demonstrated importance of oxidative phosphorylation in the active transport of potassium (33 , 54). Welt and his associa tes (5961) have implicated defective func tioning of membrane adenosine triphosphatase (A TPase) as a probable cause of the loss of K by Mg-deficient cells. On the basis of the biochemical work on subcellular membrane particles that showed that Na• -J<> -ATPase is Mg-dependent and is involved in the t ransport of Na+ and K', they concluded that magnesium is necessary for the action of "pump" ATPase. Without its optimal activity, the cells apparently Jose the capacity to maintain an appropriate concentration gradient across the cell membranes (table 1). Skou (4952), first utilizing microsomes from crab nerves and then from mammalian brain and kidney preparations, showed that Mlf is necessary for the activity of ATPase in active transport of Na• and K'" across an electrochem ical gradient. Post eta/. (38) using eryth rocyte membranes showed that both Na• and K' -dependent and independent ATPases are activated by Mlf. Dunham and Glynn ( I S, 19) have also demonstra ted that the ATPases require Mlf for full activity, and that Na+ -K'" -ATPase is direc tly involved in the ionic pump . The presence of Mg-dependent, Na•-K'-ATPase has been demonstra ted in cardiac microsomes by Auditore and Murray ( 1, 2) and by Sch wa rtz and Laseter (42, 44).