Renal Potassium Handling and Associated Inherited Tubulopathies Leading to Hypokalemia

Regulation of intracellular and extracellular potassium concentration is a fundamental process vital for cellular metabolism. Potassium intake, from the diet, is carefully balanced with excretion of potassium via the renal tract and gastrointestinal losses. Following a potassium load, extra-renal buffering of potassium occurs in peripheral tissues prior to its excretion. Thus potassium regulation is achieved by both short term and long term mechanisms. It has become clear that a series of potassium ion channels and transporter proteins have physiologically important roles throughout the length of the nephron. Our knowledge of normal physiological mechanisms has been increased by studying molecular defects responsible for variety of disorders associated with potassium transport. Studying renal tubular epithelial cell proteins and their regulation has improved the understanding of inherited tubular disorders which may cause hypokalemia. Here, we review the normal renal tubular handling of potassium and discuss the molecular basis of clinical syndromes associated with hypokalemic alkalosis and hypokalemic forms of hypertension.