The kidney maintains electrolyte and fluid balance with great precision. Under basal conditions, almost all filtered Na+ is reabsorbed in the renal tubules. The Na+,K+-ATPase pump, localized to the basolateral membranes, is the active step of this process, providing the energy for the vectorial transport of electrolytes and solutes across the epithelial cells at the cost of ATP hydrolysis. Na+ reabsorption is a dynamic process under the influence of local and humoral factors which can cause several-fold variations in Na+ excretion. Imperfect regulation of Na+ homeostasis results in disturbances in electrolyte balance of significant clinical importance. Revealing the molecular mechanisms underlying the regulation of natriuresis is of prime importance in understanding the pathogenesis o,f and directing specific therapy for, diseases such as hypertension. Here we present a model in which a cascade of intracellular events results in a bidirectional modulation of Na+,K+-ATPase activity through regulation of its phosphorylation and dephosphorylation.
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