Removal of divalent cations in cardiac Purkinje fibers causes intracellular Na+ loading via Ca2+ channels, implicating Na+-Ca2+ exchange in the etiology of the calcium paradox.
Sheep cardiac Purkinje fibers were exposed to solutions free of divalent cations for hour-long periods, while intracellular Na+ and K+ activities were measured using ion-sensitive microelectrodes. Intracellular Na+ activity (aiNa) increased to 50.1 +/- 8.1 mM, and intracellular K+ activity (aiK) decreased to 76.7 +/- 3.5 mM. These ionic changes could be blocked by the presence of Mg2+ or the Ca2+ channel blocking agents D 600 and nifedipine. The rise in aiNa and the fall in aiK was accentuated by the inhibition of the Na+-K+ pump with acetylstrophanthidin or by removal of extracellular K+. These results demonstrate that in cardiac Purkinje fibers removal of divalent cations produces intracellular loading of Na+ by Na+ entry through the Ca2+ channel. On reexposure to Ca2+-containing solutions, the cells become loaded with Ca2+, and the fibers exhibit large contractures. These observations implicate Na+-Ca2+ exchange in the entry of Ca2+ into these cells during Ca2+ repletion and in the etiology of the calcium paradox.
Chapman et al. (Mon,) studied this question.