INTRINSIC CONTROL OF THE EPITHELIAL Na+ CHANNEL (ENaC) BY PURINERGIC SIGNALING IN THE MAMMALIAN COLLECTING DUCT

The kidneys control reabsorption and excretion of water and electrolytes. This ability is pivotal for maintaining plasma volume and, thus, blood pressure (BP). Improper handling of a particular electrolyte, such as Na+, results in many diseases associated with hypo- or hypervolemia. Sodium reabsorption at the distal part of the renal nephron Z nalizes plasma Na+ levels. ENaC is localized at the apical plasma membrane of principal cells, where its activity is rate limiting for sodium movement across epithelial barriers. ENaC is a highly Na+-selective, non-voltage gated, non-inactivating ion channel in the ENaC-Deg superfamily (Benos and Stanton, 1999). It is a heteromeric channel comprised of three distinct but similar subunits: α, β, and γ having stoichiometry of 1:1:1. ENaC activity is under tight control of systemic hormones via the renin-angiotensinldosterone system (RAAS). The physiological importance of ENaC to negative-feedback regulation of blood pressure in humans is emphasized by inheritable forms of severe hypertension resulting from gain of function mutations in the channel. In contrast, loss of function mutations leads to salt wasting and low blood pressure (Schild, 1996).