Chapter 9 cAMP-Mediated Regulation of Amiloride-Sensitive Sodium Channels: Channel Activation or Channel Recruitment?

Abstract

Publisher Summary The chapter presents a discussion on the mechanisms, whereby intracellular cyclic adenosine monophosphate (cAMP) increases amiloride-sensitive sodium ion (Na + ) channel activity. In some tissues, such as the rat distal colon and human nasal epithelia amiloride-sensitive Na + channel activity is not stimulated by CAMP. The peptide hormone vasopressin and its analogs, vasotocin and oxytocin, increase amiloride-sensitive Na + transport across mammalian collecting ducts and amphibian epithelia (that is, toad urinary bladder, frog skin and colon, and Xenopus A6 renal epithelial cells) two- to fourfold through an increase in intracellular cAMP. This increase in Na + transport develops rapidly over a period of 5–30 minutes and is initiated by the binding of vasopressin to V 2 receptors situated in the basolateral membrane. This in turn leads to the stimulation of adenylate cyclase via the heterotrimeric G protein, Gα s , and a concomitant increase in intracellular cAMP, which results in increased Na + channel activity. The fact that membrane-permeable cAMP analogs, inhibitors of phosphodiesterase, and activators of adenylate cyclase, all mimic the vasopressin induced activation of amiloride sensitive Na + channels clearly indicates that the action of vasopressin is mediated by cAMP. The chapter summarizes the data supporting activation of quiescent channels through a protein kinase A (PKA) mediated phosphorylation of a channel subunit or an associated regulatory protein.