Guanine nucleotide binding proteins regulate epithelial Na+ channels.

Abstract

Regulation of ion movements via transport proteins is of particular importance in absorbing and secreting epithelia where the intracellular ionic concentrations must be carefully balanced to enable the cells to perform transepithelial electrolytic movements. The ability of epithelia to respond in an acute fashion to environmental signals relies, in part, on their capacity to induce a set of secondary messengers, including the intracellular signals Ca2+, pH and cAMP, generated by interaction of hormones with receptors at the basolateral membrane (1). The resultant physiological response at the apical membrane (e.g. increased Na+ transport) is assumed to develop from the transmission of these second messenger systems through, for example, protein kinases in biochemical pathways which result in the phosphorylation of one or more apical membrane proteins, including the Na+ channel itself (2). Recent evidence from studies of partially purified Na+ channels from the apical membrane of A6 cells suggest that one of the proteins in this complex (of at least 7 proteins) is phosphorylated by cAMP-dependent protein kinase (3). Changes in the intracellular cAMP concentration upon activation of the V2 receptor by vasopressin have been reported to increase Na+ transport in tight epithelia, such as toad urinary bladder and the A6 toad kidney cell line (4,5).