MANIPULATION OF INTRACELLULAR SODIUM BY EXTRACELLULAR DIVALENT-CATIONS - A NA-23 AND P-31 NMR-STUDY ON INTACT RAT HEARTS

Na-23 and P-31 NMR spectroscopy were used to follow intracellular [Na] ([Na+](i)) and energy metabolism in isolated, perfused rat hearts, D uring 30 min of Ca2+-free perfusion no significant change in [Na+](i) could be detected, but during a subsequent 45 min period of ischemia [ Na+](i) rose significantly as expected, from 8.6+/-2.4 to 36.8+/-9.4 m M. In contrast, already during 30 min of Ca2+-and Mg2+-free perfusion [Na+](i) rose significantly from 7.3+/-3.7 to 71.3 +/-15.6 mM. During this period, the Na+-K+ ATPase was not limited by depletion of high en ergy phosphates, decrease of intracellular free Mg2+ or accumulation o f inorganic phosphate, During the first 8 min of a subsequent period o f ischemia, the rate of rise in [Naf], even 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 larg e Na+-influx, Using verapamil, we could demonstrate that this large Na +-influx occurs through the L-type Ca2+ channels, and that both Mg2+ a nd verapamil can block this Na+-influx. Previously, we have demonstrat ed that [Na+](i) does not play a role in the origin of the calcium par adox. The notion that an increased [Na+](i) is a prerequisite for the calcium paradox to occur apparently results from experimental evidence obtained under conditions of low or absent Mg2+. (C) 1998 Academic Pr ess Limited.