From the Research
The Na+/K+ ATPase does not directly create a chloride (Cl-) gradient but contributes indirectly through its establishment of the sodium gradient, as supported by the most recent study 1. The Na+/K+ ATPase pumps three sodium ions out of the cell while bringing two potassium ions in, consuming one ATP molecule in the process. This creates a sodium gradient that secondary transporters can utilize. For chloride specifically, the sodium gradient powers Na+-K+-2Cl- cotransporters (NKCC) that move chloride into cells against its concentration gradient. Additionally, the negative membrane potential established partly by the Na+/K+ ATPase creates an electrical driving force that influences chloride distribution according to the Nernst equation. In some epithelial cells, chloride can exit the apical membrane through chloride channels, completing transcellular chloride transport. This mechanism is particularly important in tissues like the kidney, where chloride reabsorption is critical for maintaining electrolyte balance. Dysfunction in this system can lead to disorders like cystic fibrosis, where impaired chloride transport causes thick secretions in multiple organs, as discussed in 2, 3, 4. The structure and function of Na,K-ATPase have been extensively studied, and its vital physiological role in essentially every cell has been established, as reviewed in 4. Furthermore, the Na+/K+-ATPase also functions as a receptor for cardiac glycosides like ouabain, triggering the activation of various signaling pathways, as reported in 1. Overall, the Na+/K+ ATPase plays a crucial role in maintaining electrolyte balance and proper cellular function, and its dysfunction can have significant consequences for morbidity, mortality, and quality of life.