Pumping Ratio of the Na + /K + Pump — A Further View

Abstract

Our current knowledge about the Na⁺/K⁺ pump is mainly of the structure and function of the pump itself. The knowledge of the relationship between the function of the pump and other cellular functions is inadequate. This is because we are unaware of what the pumping process is and why the pump takes 3 Na⁺ to 2 K⁺ as the pumping ratio. In recent years, I proposed a dipole-charging model to simulate the pumping process of the Na⁺/K⁺ pump and showed by this model that this pumping ratio of the Na⁺/K⁺ pump is determined by the ratio of the ionic mobilities of K⁺ to Na⁺ ions. In this article, I further propose an osmotic balance condition that the potassium ion concentration inside the cell and the sodium ion concentration outside the cell are equal. With this condition, the dipole-charging model is further extended to compare different pumping ratios and it shows that only the pumping ratio 3 Na⁺ to 2 K⁺ can be selected during evolution. This result also reveals the relationships between the 3 Na⁺ to 2 K⁺ pumping ratio, the membrane resting potential, and the osmotic balance condition of the cell. Furthermore, I discuss the osmotic balance condition, the stability of the dipole-charging model and the dipole-charging process, the electrogenic contribution by the Na⁺/K⁺ pump to the resting membrane potential, and the effectiveness and the prospect of the dipole-charging model. The dipole-charging model is capable of explaining all the phenomena related to the pumping process of the Na⁺/K⁺ pump and is especially suitable for study in situations under pathologic conditions, such as ischemia or hypoxia. Finally, I present analyses of the free energy change of the coupled overall reaction for the Na⁺/K⁺ pump and of some reports on different pumping ratios of the Na⁺/K⁺ pump. The exception of the pumping ratio in the brine shrimp Artemia is also discussed.