Epithelial Na Channels : Why All the Subunits?

Epithelial Na channels mediate Na reabsorption in the distal segments of the kidney, gut, and other organs (Garty and Palmer, 1997). They are vital to the control of blood volume and arterial blood pressure, as evidenced by various forms of hypertension involving defects in the channels themselves or the renin–angiotensin–aldosterone axis regulating them (Lifton, 1996). Several years ago the molecules comprising these channels were cloned and sequenced (Canessa et al., 1993; Lingueglia et al., 1993; Canessa et al., 1994). The first clone, called αrENaC, was sufficient to produce amiloride-sensitive Na currents when expressed in Xenopus oocytes. The physiological and pharmacological properties of these channels resembled those in the kidney and other native epithelia, but the magnitude of the currents was small. Much larger currents were obtained when αrENaC was coexpressed with two additional subunits termed βrENaC and γrENaC. The β and...