**2. Regulation of potassium excretion at the distal tubular site**

More than 98% of total body potassium is located inside the cells and homeostatic control of extracellular potassium by the intracellular pool is critical in the regulation of plasma potassium concentration. Plasma potassium levels are maintained stable between 3.5 and 5.0 mEq/l despite remarkable variability in potassium intake with meals. This balance is due to mechanisms that operate principally at the renal level and regulate potassium excretion. In normal conditions, daily intake of potassium is entirely eliminated by the body, 90% by the kidney and 10% by the intestine. Therefore, changes in body potassium content are physiologically regulated by the kidney that compensates with increased reabsorption in conditions of hypokalemia, and increased secretion in conditions of hyperkalemia. Potassium transport occurs along the entire nephron, but the major role in potassium secretion is played at the distal site by the connecting tubule and cortical collecting duct. In these sites, principal cells are responsible for regulation of sodium reabsorption and via the amiloride-sensitive epithelial sodium channel (ENaC) (Figure 2) with the associated potassium and hydrogen ion excretion. Sodium entry via ENaC generates an excess of negative charges in the tubular lumen that causes intracellular potassium to leave the cell through the renal outer medullary K channel (ROMK) and the flow-sensitive maxi-K potassium channel (BK K+) (Figure 2). In addition to distal sodium reabsorption through the ENaC, potassium secretion is therefore dependent on distal tubular flow. Aldosterone has direct influence on potassium secretion, activating sodium transport through activation of the ENaC and increasing the driving force for potassium secretion into the tubular lumen (Figure 3).
