Manipulation of Intracellular Sodium by Extracellular Divalent Cations: a23Na and31P NMR Study on Intact Rat Hearts

23Na and31P NMR spectroscopy were used to follow intracellular [Na+] ([Na+]i) and energy metabolism in isolated, perfused rat hearts. During 30 min of Ca2+-free perfusion no significant change in [Na+]icould be detected, but during a subsequent 45 min period of ischemia [Na+]irose significantly as expected, from 8.6±2.4 to 36.8±9.4 m . In contrast, already during 30 min of Ca2+- and Mg2+-free perfusion [Na+]irose significantly from 7.3±3.7 to 71.3±15.6 m . During this period, the Na+–K+ ATPase was not limited by depletion of high energy phosphates, decrease of intracellular free Mg2+or accumulation of inorganic phosphate. During the first 8 min of a subsequent period of ischemia, the rate of rise in [Na+]ieven increased, suggesting that during the preceding period of Ca2+- and Mg2+-free perfusion, the Na+–K+ ATPase was indeed operative but apparently not coping with the large Na+-influx. Using verapamil, we could demonstrate that this large Na+-influx occurs through the -type Ca2+channels, and that both Mg2+and verapamil can block this Na+-influx. Previously, we have demonstrated that [Na+]idoes not play a role in the origin of the calcium paradox. The notion that an increased [Na+]iis a prerequisite for the calcium paradox to occur apparently results from experimental evidence obtained under conditions of low or absent Mg2+.