A molecularly guided tour along the nephron

Abstract

The kidney is an intriguingly multifaceted organ controlling many vital body functions. Therefore, the kidney orchestrates a large set of tasks including the maintenance of the body fluid balance and thereby the blood pressure, the reabsorption of glucose, amino acids and other nutrients, the excretion of sodium, potassium, calcium, magnesium, and other electrolytes, and the control of the acid/base balance. In addition, the kidney produces hormones and proteins exerting important general physiological roles. For instance, the biological active form of vitamin D is mainly produced in the kidney through the conversion of 25hydroxyvitamin D3 to 1,25-dihydroxyvitamin D3 by the renal enzyme 25-hydroxyvitamin D-1-α-hydroxylase. In addition, the antiaging hormone klotho is primarily produced in the kidney and controls overall mineral metabolism. Also, the glycoprotein erythropoietin is generated here and enhances the oxygen-carrying capacity of the blood by activating the production of erythrocytes by the bone marrow. The importance of these renal hormones is sadly demonstrated by the severe symptoms accompanying chronic kidney diseases. The kidney is an anatomically complex structure consisting of a large number of nephrons, the functional units of the kidney. Each nephron begins with a glomerulus that filters blood entering the kidney. This filtrate then flows along the length of the nephron. The major function of the epithelial cells lining the nephron is the reabsorption of water and small molecules from the filtrate into the blood and the secretion of wastes from the blood into the urine. To this end, the kidney is equipped with a host of transport proteins including ion channels, electrolyte transporters, and pumps within specific epithelial cells along the various tubule segments. In recent years, our understanding of the molecular nature of these transport proteins has made major progress through the application of functional expression cloning techniques using Xenopus laevis oocytes and the identification of gene defects in inherited renal tubular transport disorders. The regulation of these transport processes is constantly challenged by a demanding and greatly variable environment including an acidic luminal pH, a high medullary osmolarity, and a variability in blood and urinary flow as well as in the composition of the prourine [4]. The activity of these transporters can basically be controlled at several discrete levels. First, the expression level of the particular transporter can be regulated by specific hormones. Second, trafficking of the transporter to the designated plasma membrane can be controlled by intracellular signaling processes. Third, the activity of the transport protein present at the plasma membrane can be subject to various extra-en intracellular regulatory mechanisms. Ample timely physiological studies have addressed these various regulatory aspects of renal transport processes. New key physiological mechanisms have emerged from these recent investigations particularly through a multidisciplinary approach using model cells and organisms. The complexity in structure and function of the kidney is increasingly revealed by these investigations. To do justice to this fact, a standard nomenclature has been disseminated to facilitate the renal physiologist [14]. Consequently, this special issue has been divided according to the main parts of the nephron including the proximal tubule, the loop of Henle, the distal convoluted tubule, the connecting tubule, and the collecting duct. In this guided tour along the nephron, world-renowned renal physiologists highlight the Pflugers Arch Eur J Physiol (2009) 458:1–3 DOI 10.1007/s00424-009-0661-3