Regulation of Renal Outer Medullary Potassium Channel and Renal K Excretion by Klotho

Klotho is an aging-suppression protein predominantly ex-pressed in kidney, parathyroid glands, and choroids plexus of the brain. The extracellular domain of Klotho, a type-1 mem-brane protein, is secreted into urine and blood and may func-tion as an endocrine or paracrine hormone. The functional role of Klotho in the kidney remains largely unknown. Recent stud-ies reported that treatment by the extracellular domain of Klotho (KLe) increases cell-surface abundance of transient re-ceptor potential vanilloid type isoform 5, an epithelial Ca2 channel critical for Ca2 reabsorption in the kidney. Whether Klotho regulates surface expression of other channels in the kidney is not known. Here, we report that KLe treatment in-creases the cell-membrane abundance of the renal K channel renal outer medullary potassium channel 1 (ROMK1) by remov