Calcium paradox of the heart: a role for intracellular sodium ions

Abstract

Hearts that have been perfused in low calcium fluids suffer, on return to normal calcium solutions, an impairment of function which can be irreversible-- the "calcium paradox." In hypothermic mammalian, amphibian, and fish heart the strong contracture, which is a typical first stage in the development of the calcium paradox, is reversible and appears to depend on a large rise in intracellular Na concentration ([Na]i), which occurs during the period of Ca deprivation. This rise is mainly due to a maintained inward Na flux through the Ca channels and causes a depolarization of the membrane potential, which stabilizes at about -20 mV. In frog atrial muscle if the membrane potential is clamped to values more negative than -50 mV during the period of Ca deprivation, no contracture develops on the restoration of the extracellular Ca concentration ([Ca]o). In all tissues the depolarization, the rise in [Na]i, and the Ca addition contracture are blocked by Ca channel blockers, antiarrhythmic drugs, and Mg ions if present in the Ca-free fluid. These agents are ineffective, however, if applied after a period of Ca deprivation when [Na]i has already risen. The influx of Ca ions, on Ca repletion, is therefore unlikely to be via the Ca channels and would seem to be through the Na-Ca exchange.