Going with the flow: New insights regarding flow induced K+ secretion in the distal nephron.

Abstract

K⁺ secretion in the distal nephron has a critical role in K⁺ homeostasis and is the primary route by which K⁺ is lost from the body. Renal K⁺ secretion is enhanced by increases in dietary K⁺ intake and by increases in tubular flow rate in the distal nephron. This review addresses new and important insights regarding the mechanisms underlying flow-induced K⁺ secretion (FIKS). While basal K⁺ secretion in the distal nephron is mediated by renal outer medullary K⁺ (ROMK) channels in principal cells (PCs), FIKS is mediated by large conductance, Ca²⁺/stretch activated K⁺ (BK) channels in intercalated cells (ICs), a distinct cell type. BK channel activation requires an increase in intracellular Ca²⁺ concentration ([Ca²⁺]_i), and both PCs and ICs exhibit increases in [Ca²⁺]_i in response to increases in tubular fluid flow rate, associated with an increase in tubular diameter. PIEZO1, a mechanosensitive, nonselective cation channel, is expressed in the basolateral membranes of PCs and ICs, where it functions as a mechanosensor. The loss of flow-induced [Ca²⁺]_i transients in ICs and BK channel-mediated FIKS in microperfused collecting ducts isolated from mice with IC-specific deletion of Piezo1 in the CCD underscores the importance of PIEZO1 in the renal regulation of K⁺ transport.