Calculation of the Reversal Potential of the Na+/Ca++ Exchanger Through the Time Course of the Calcium Paradox: A Model Study

Abstract

The mode of action of the Na/Ca exchanger was calculated during calcium paradox injury. Several different conditions were assumed and the resulting reversal potential was calculated continuously according to the following equation: E_{Na-Ca} = 3*E_{Na}-2*E_{Ca}. The variables were The intracellular Na+ and Ca++ concentrations, and the membrane potential. In the calculations, various combinations of the variable parameters were selected to simulate the most actual conditions during a Ca-Paradox experiment. The possible role of the Na/Ca exchanger in the ethiopathogenesis of the Ca-Paradox injury, or rather whether the exchanger could be involved in the production of the Ca overload observed in reperfused hearts, is investigated. At rest the driving force indicates a net extrution of calcium ions via the Na/Ca exchanger. The exchanger is said to be in the ÒexitÕ mode. As the cell depolarizes, the membrane potential approaches the reversal potential for the exchanger. When the membrane potential is equal to the reversal potential, the exchanger does not cause any net counter transport of ions. If the cell depolarizes further, the exchanger brings calcium into the cell from the extracellular space. Hence, the exchanger is said to be in the ÒentryÓ mode. In the calculations, the mode of action of the exchanger was calculated in response to the changes in the participating potentials Em, ENa, ECa. However, in most of the assumed conditions, the exchanger was calculated to be in the exit mode, indicating a removal of calcium rather than an overload. This study points out that theoretically the exchanger alone may not explain the Ca-overload observed in the reperfused hearts in Ca-Paradox experiments.