Regulatory mechanism of “K+-recycling” for Na+-reabsorption in renal tubules

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Hypertension is one of the predominant risk factors for the progression of renal impairment, and the most common disorder in industrialized societies. Because reduction of the systemic blood pressure in hypertension can halt the progression of renal impairment, it is imperative to appropriately control the systemic blood pressure. Recent genetic analysis has reconfirmed that renal maladjustment of Na+-homeostasis, which determines the extracellular fluid volume, is a key element in the pathogenesis of hypertension. The distal tubules adjust the net Na+-excretion according to Na+-ingestion and maintain the Na+-homeostasis. The distal convoluted tubules and the connecting tubules are the predominant sites for the adjustment in individuals with a modern lifestyle. In these tubules, Na+-reabsorption depends on “K+-recycling”, which is conducted through K+ channels. Because the functional expression of K+ channels in these tubules is regulated by signal motifs for intracellular localization, the adjustment of “K+-recycling” through the modification of signal motifs could be a new target for the treatment of hypertension.

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