DIVERSITY AND REGULATION OF AMILORIDE-SENSITIVE NA+ CHANNELS

Amiloride-sensitive Na+ channels play a vital role in many important p hysiological processes such as delineation of the final urine composit ion, sensory transduction, and whole-body Na+ homeostasis. These chann els display a wide range of biophysical properties, and are regulated by cAMP-mediated second messenger systems. The first of these channels has recently been cloned. This cloned amiloride-sensitive Na+ channel is termined ENaC (Epithelial Na+ Channel) and, in heterologous cellul ar expression systems, displays a single channel conductance of 4 to 7 pS, a high P-Na/P-K (> 10), a high amiloride sensitivity (K-i(amil) = 150 nM), and relatively long open and closed times. ENaC may form the core conduction element of many of these functionally diverse forms o f Na+ channel. The kinetic and regulatory differences between these ch annels may be due, in large measure, to unique polypeptides that assoc iate with the core element, forming a functional channel unit.