Focus on “Contrasting effects of cPLA2 on epithelial Na+ transport”

THE AMILORIDE-SENSITIVE epithelial Na channel (ENaC) plays a central role in the reabsorption of salt and fluids across Na -reabsorbing epithelia such as the distal nephron, distal colon, lungs, and ducts of the exocrine glands. ENaC is rate limiting for net Na reabsorption because it mediates entry of Na from the luminal fluid during the first stage of electrogenic Na transport (1, 9). Thus ENaC plays a key role in the regulation of fluid and electrolyte homeostasis and blood pressure. Malfunction or mutations of ENaC are associated with a number of human diseases such as Liddle's syndrome, an inherited form of arterial hypertension, pseudohypoaldosteronism type 1, pulmonary edema, cystic fibrosis, and influenza Because of its central role in transepithelial fluid transport, the activity of ENaC is highly regulated by hormones such as aldosterone, vasopressin, and insulin, extracellular proteases, accessory proteins, and intracellular mediators such as Na , Ca 2 , pH, and protein kinases A and C (1, 9). The regulation of ENaC activity occurs at two major levels: 1) at the level of the membrane [i.e., modulation of the number of active channels (channel density)]; and 2) at the level of the channel itself [i.e., modulation of single channel open probability (P o )].