Renal potassium homeostasis: a short historical perspective

During the past century, investigators have increased our understanding of renal potassium excretion significantly using many techniques. Notable among these were renal clearance experiments, renal micropuncture, isolated tubule microperfusion, and electrophysiological and patch clamp analysis. These experiments have been made possible by technical advances that have allowed the measurement of potassium in progressively smaller quantities. Initially, the kidney was viewed as controlling potassium excretion by the regulated absorption of potassium from the glomerular filtrate, predominantly in the proximal tubule. This concept was supplanted when clearance experiments deduced and subsequent micropuncture studies directly identified the importance of the distal nephron and collecting duct as the principal site responsible for the regulation of potassium excretion. Additional micropuncture and microperfusion studies showed that a component of potassium secreted by the distal cortical nephron and cortical collecting duct is reabsorbed in the medullary collecting duct, which results in renal medullary potassium recycling. Studies have defined the cellular and molecular mechanisms responsible for potassium secretion and potassium reabsorption in the collecting duct. Further understanding of renal potassium handling will require integrated investigation of the renal and extrarenal signaling systems that control these transport mechanisms.